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Programmed cell death (PCD) plays an important role in many aspects of individual development, maintenance of body homeostasis and pathological processes. Ferroptosis is a novel form of PCD characterized by the accumulation of iron-dependent lipid peroxides resulting in lethal cell damage. It contributes to tumor progression in an apoptosis-independent manner. In recent years, an increasing number of non-coding RNAs (ncRNAs) have been demonstrated to mediate the biological process of ferroptosis, hence impacting carcinogenesis, progression, drug resistance, and prognosis. However, the clear regulatory mechanism for this phenomenon remains poorly understood. Moreover, ferroptosis does not usually exist independently. Its interaction with PCD, like apoptosis, necroptosis, autophagy, pyroptosis, and cuproptosis, to destroy cells appears to exist. Furthermore, ncRNA seems to be involved. Here, we review the mechanisms by which ferroptosis occurs, dissect its relationship with other forms of death, summarize the key regulatory roles played by ncRNAs, raise relevant questions and predict possible barriers to its application in the clinic, offering new ideas for targeted tumour therapy. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, the most prevalent cancer-related death worldwide, still lacks the means for early diagnosis. Because of the unique properties of the loop that make it stable in body fluids, circular RNAs (circRNAs) as a biomarker becomes a possibility. This research purposed to explore whether hsa_circ_0023179 can be applied as a possible biomarker for the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). Methods: hsa_circ_0023179 was screened by high-throughput sequencing of three pairs of NSCLC tissues and their surrounding tissues. Agarose gel electrophoresis (AGE), Sanger sequencing, exonuclease digestion assay, and actinomycin D were used to affirm the molecular properties of circRNA. Precision determination was performed by placement at room temperature and multiple freeze–thawing test for methodological evaluation. The expression of hsa_circ_0023179 in tissues, serum, and cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) to establish the receiver operating characteristic (ROC) curve to assess the diagnostic efficacy of hsa_circ_0023179. Results: hsa_circ_0023179 conforms to the basic properties of circRNA, and the detection method of hsa_circ_0023179 has good stability and repeatability. Its expression was connected to histological type, TNM stage, lymph node metastasis, and distal metastasis in NSCLC tissues, serum, and cells. Compared with traditional tumor markers with higher sensitivity and specificity. A combined diagnosis can significantly improve the diagnostic value. The decrease in postoperative expression level suggests some potential for dynamic monitoring. Conclusion: hsa_circ_0023179 might be a promising novel serum marker for the detection and prediction of NSCLC. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptors (GPCRs) are the most prominent family of cell surface receptors, which can regulate various biological functions and play an essential role in many diseases. GPR176 is a member of the GPCRs family and has been rarely studied in cancer. We aim to investigate the diagnostic and prognostic value of GPR176 in gastric cancer (GC) and explore its potential mechanism. Through the TCGA database and real-time quantitative PCR, we found that the expression level of GPR176 was significantly increased in GC and had good value in the diagnosis and prognosis of GC. Vitro experiments revealed that GPR176 could promote the proliferation, migration, and invasion of GC cells and may be involved in regulating multiple tumors and immune-related signaling pathways. In addition, we found that GPR176 is associated with GC immune infiltration and may affect the immune efficacy of GC patients. In summary, the high GPR176 expression level was associated with poor prognosis, more robust immune infiltration, and worse immunotherapy efficacy in GC patients, suggesting that GPR176 may be an immune-related biomarker for GC that can promote the proliferation, migration, and invasion of GC cells. [ABSTRACT FROM AUTHOR]

Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays. TUG1 knockdown reduced the cell's proliferative and migratory capabilities while increasing apoptosis and bortezomib sensitivity in vitro and inhibiting tumorigenesis in vivo. TUG1 was found in the nucleus of MM cells and was found to be positively regulated by the TF-YY1. Further in vitro mechanistic investigations indicated that the YY1-TUG1 complex targeted YOD1 to regulate MM progression. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have become a research hotspot in recent years with their universality, diversity, stability, conservativeness, and spatiotemporal specificity. N6-methyladenosine (m6A), the most abundant modification in the eukaryotic cells, is engaged in the pathophysiological processes of various diseases. An increasing amount of evidence has suggested that m6A modification is common in circRNAs and is associated with their biological functions. This review summarizes the effects of m6A modification on circRNAs and their regulation mechanisms in cancers, providing some suggestions of m6A-modified circRNAs in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers. Methods: The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan–Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC. Results: Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan–Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells. Conclusions: The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients. [ABSTRACT FROM AUTHOR]

Background. Gastric cancer (GC) is a malignant tumor of the gastrointestinal system. Since the early symptoms of GC are not obvious and lack efficient diagnostic markers, it is urgent to find new diagnostic markers with good sensitivity and specificity. tRNA-derived small RNAs (tsRNAs) are an emerging class of small noncoding RNAs with good abundance in body fluids. We aim to find new tsRNAs as biomarkers for GC diagnosis. Methods. High-throughput sequencing was used to identify differentially expressed tsRNAs in GC tissues, and quantitative real-time PCR was used to detect the expression level of tRF-17-WS7K092. Agarose gel electrophoresis and Sanger sequencing were performed to verify the characteristics of tRF-17-WS7K092. The diagnostic efficacy of tRF-17-WS7K092 was analyzed by the receiver operating characteristic curve. Results. In this study, the expression levels of tRF-17-WS7K092 were significantly increased in GC tissues, cells, and serum. After GC surgery, the expression level of serum tRF-17-WS7K092 decreased, and its high expression was associated with low survival rates. In addition, the expression level of serum tRF-17-WS7K092 was correlated with the T stage, TNM stage, lymph node metastasis, and nerve/vascular invasion and could distinguish GC patients from gastritis patients and healthy donors as well. Conclusions. The expression of serum tRF-17-WS7K092 was significantly increased in GC and decreased after GC surgery, suggesting that serum tRF-17-WS7K092 may serve as a promising biomarker for the diagnostic and prognostic monitoring of GC. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mitochondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments. Methods: A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC. Results: The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell proliferation and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3′-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellular DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, promote DOX accumulation, and reverse DOX resistance. Conclusions: Our results demonstrated that circ_0000098 is an oncogenic circRNA that promotes HCC development through the miR-383/MCUR1 axis and targeting circ_0000098 with DOX/sh-1@PLT may be a promising and practical therapeutic strategy for preventing DOX resistance in HCC. [ABSTRACT FROM AUTHOR]

Transfer RNAs (tRNAs) promote protein translation by binding to the corresponding amino acids and transporting them to the ribosome, which is essential in protein translation. tRNA-derived small RNAs (tsRNAs) are derived fragments of tRNAs that are cleaved explicitly under certain conditions. An increasing amount of research has demonstrated that tsRNAs have biological functions rather than just being degradation products. tsRNAs can exert functions such as regulating gene expression to influence cancer progression. Their dysregulation is closely associated with various cancers and can serve as diagnostic and prognostic biomarkers for cancer. This review summarizes the generation, classification, and biological functions of tsRNAs, and highlights the roles of tsRNAs in different cancers and their applications as tumor markers. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P < 0.001). CCAT2 relative expression was positively correlated with tumor Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag and lymph node metastasis (LNM) (all P < 0.05). CCAT2 expression in recurrent/metastatic CC was significantly higher compared with primary CC (P < 0.0001) or operated CC (P < 0.0001) and during follow-up, CCAT2 expression was increased before surgery and decreased significantly after surgery (P < 0.0001). Furthermore, the overall survival rate of CC patients with high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = 0.026). Univariate analyses indicated that CCAT2 was a poor prognostic factor associated with overall survival (OS). Our study indicates that CCAT2 may be valuable in complementary diagnosis and monitoring of progression and prognosis of CC patients. Combined detection of CCAT2, CA125 and SCC can greatly improve the diagnostic efficiency of primary CC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It's particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned. [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised. Methods: We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays. Results: Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson's R = − 0.43, P < 0.001) between promoter methylation and CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1. Conclusions: Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors. Method: Using circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit‐8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression. Result: CircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs. Conclusion: CircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway. [ABSTRACT FROM AUTHOR]

Increasing knowledge of long non-coding RNAs (lncRNAs) has shown that they can be used as circulating tumor markers. Also, considerable evidences have revealed that lncRNAs have important roles in tumor diagnosis and prognosis. The lncRNA CCAT2 has manifested its carcinogenic effect in a variety of tumors, but the serum expression level and clinical value in multiple myeloma (MM) remain to be explored. In our study, the expression of lncRNA CCAT2 is upregulated in the serum and bone marrow of MM patients by using quantitative real-time polymerase chain reaction (qRT-PCR). The high expression level of CCAT2 in the serum of MM patients correlated with International Scoring System (ISS) stages, renal dysfunction, serum β2-microglobulin (β2-MG) concentration, and light chain (κ and λ) concentrations. Area under the curve (AUC) of CCAT2 in serum is 0.899. Besides, the sensitivity and specificity were 85.80% and 83%, respectively. Furthermore, combination of CCAT2, IgA, HGB, and β2-MG significantly improved the MM diagnostic sensitivity and AUC. Here, our present investigation indicates that serum circulating CCAT2 may serve as a potential tumor marker for diagnosis and prognosis of MM. [ABSTRACT FROM AUTHOR]

Targeted treatment, which can specifically kill tumour cells without affecting normal cells, is a new approach for tumour therapy. However, tumour cells tend to acquire resistance to targeted drugs during treatment. Circular RNAs (circRNAs) are single-stranded RNA molecules with unique structures and important functions. With the development of RNA sequencing technology, circRNAs have been found to be widespread in tumour-resistant cells and to play important regulatory roles. In this review, we present the latest advances in circRNA research and summarize the various mechanisms underlying their regulation. Moreover, we review the role of circRNAs in the chemotherapeutic resistance of tumours and explore the clinical value of circRNA regulation in treating tumour resistance. [ABSTRACT FROM AUTHOR]

In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A is installed by m6A methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA and ZC3H13, termed "writers"), removed by demethylases (FTO, ALKBH5, and ALKBH3, termed "erasers"), and recognized by m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, and eIF3, termed "readers"). Accumulating evidence suggests that m6A RNA methylation greatly impacts RNA metabolism and is involved in the pathogenesis of many kinds of diseases, including cancers. In this review, we focus on the physiological functions of m6A modification and its related regulators, as well as on the potential biological roles of these elements in human tumors. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have emerged as important roles in gastric cancer (GC). However, the role of the dysregulated lncRNAs in GC remained large unknown. We investigated the clinical significance, biological function and mechanism of CTC-497E21.4 in GC. Methods: Firstly, RTFQ-PCR was used to detect the expression of CTC-497E21.4 in GC. Furthermore, knockdown of CTC-497E21.4 was conducted to assess the effect of CTC-497E21.4 in vitro and vivo. Subcellular localization of CTC-497E21.4 was determined by nuclear plasmolysis PCR and FISH. We also predicted CTC-497E21.4 binding miRNAs and downstream target genes and evaluated its regulation of miR-22 by acting as a ceRNA. Result: CTC-497E21.4 was upregulated in GC tissues and GC cell lines (P < 0.05), and the expression was associated with depth of invasion, lymph node metastasis, and neurological invasion. Besides, knockdown of CTC-497E21.4 inhibited cell proliferation, invasion and promoted cell cycle arrest in vitro and inhibited tumorigenesis in vivo. Mechanistic investigations indicated that CTC-497E21.4 acted as a ceRNA for miR-22 and regulated NET1 expression. CTC-497E21.4/miR-22-3p/NET1 participated in the RhoA signaling pathway in the GC progression. Conclusion: CTC-497E21.4 competed with miR-22 to regulate the expression of NET1 and regulated the malignant progression of GC through RhoA signaling pathway. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and mortality remains high, especially in East Asia. At present, the main method to diagnose gastric cancer is pathological biopsy. At the time of diagnosis, most patients have been diagnosed with advanced cancer and metastasis. The treatment of gastric cancer patients is mainly radical surgical resection and chemoradiotherapy, while patients with metastatic tumor have great challenges to radical surgery and are prone to drug resistance. Metastasis is an important factor affecting tumor development. In addition, evidence accumulated in the literature indicates that non-coding RNA plays a key role in tumor metastasis. This article reviews the role of ncRNAs in gastric cancer metastasis and discusses the regulatory mechanism in the development and treatment of gastric cancer. • ncRNAs involved in GC metastasis • ncRNAs regulates the metastasis mechanism of GC. • Application of ncRNAs in cancer diagnosis [ABSTRACT FROM AUTHOR]

• The diagnostic value of hsa_circ_0001479 in gastric cancer was evaluated. • The feedback loop based on hsa_circ_0001479 regulated the malignant progression of gastric cancer was reported. • Hsa_circ_0001479 was found to have a certain impact on the immune microenvironment. Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of β-catenin into the nucleus by activating Wnt/β-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited the infiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) exist in the peripheral blood and have an important role in the disease development, tumor metastasis and clinical surveillance, especially in the process of metastasis. However, the technology of detecting CTCs still had a large challenge since they were rare in the peripheral blood. Here, we developed a size-based microfluidic chip, which contained array and filter channel array that could enrich CTCs from blood samples more quickly and conveniently. Combined with clinical specimen, we analyzed CTCs in 200 lung cancer patients by this microfluidic chip. The microfluidic device has high specificity and sensitivity in detecting CTCs (86.0% sensitivity and 98% specificity). Furthermore, the number of CTCs showed a increasing trend according to the stage of the disease (the mean number of I stage 5.0 ± 5.121 versus II stage 8.731 ± 6.36 versus III stage 16.81 ± 9.556 versus IV stage 28.72 ± 17.39 cells/mL, P < 0.05). The number of CTCs was concurrent with the condition of pathological type and metastasis patients. Compared to conventional markers like CEA, CY211, SCC, CTCs showed a higher positive rate in diagnosed patients. The advanced microfluidic device could capture tumor cells without reliance on cell surface expression markers and provide a fast, convenient, economical method in detecting CTCs, thereby offering potential to design effective and individualized cancer therapies. [ABSTRACT FROM AUTHOR]

Background Measurement uncertainty (MU) is a metrological concept, which can be used for objectively estimating the quality of test results in medical laboratories. The Nordtest guide recommends an approach that uses both internal quality control (IQC) and external quality assessment (EQA) data to evaluate the MU. Bootstrap resampling is employed to simulate the unknown distribution based on the mathematical statistics method using an existing small sample of data, where the aim is to transform the small sample into a large sample. However, there have been no reports of the utilization of this method in medical laboratories. Thus, this study applied the Nordtest guide approach based on bootstrap resampling for estimating the MU. Methods We estimated the MU for the white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), and platelets (Plt). First, we used 6 months of IQC data and 12 months of EQA data to calculate the MU according to the Nordtest method. Second, we combined the Nordtest method and bootstrap resampling with the quality control data and calculated the MU using MATLAB software. We then compared the MU results obtained using the two approaches. Results The expanded uncertainty results determined for WBC, RBC, Hb, and Plt using the bootstrap resampling method were 4.39%, 2.43%, 3.04%, and 5.92%, respectively, and 4.38%, 2.42%, 3.02%, and 6.00% with the existing quality control data ( U [ k = 2]). For WBC, RBC, Hb, and Plt, the differences between the results obtained using the two methods were lower than 1.33%. The expanded uncertainty values were all less than the target uncertainties. Conclusions The bootstrap resampling method allows the statistical analysis of the MU. Combining the Nordtest method and bootstrap resampling is considered a suitable alternative method for estimating the MU. [ABSTRACT FROM AUTHOR]

Recombinant T2 RNase glycoprotein, which showed a certain degree of homology to Omega-1 from Schistosoma mansoni eggs, was expressed in adult worms of Schistosoma japonicum, but not in eggs of S. japonicum. The direct biological role of the recombinant T2 RNase protein in activation of hepatic stellate cells (HSCs) remains unknown. In the present study, the immortalized human HSC line (LX-2 cells) was treated with the recombinant T2 RNase protein at indicated concentrations for various time points in vitro. The expression levels of α-smooth muscle actin (α-SMA) and Smad4 were detected by Western blot. The results showed that the recombinant T2 RNase protein significantly diminished the expression levels of α-SMA and Smad4 in LX-2 cells. The upregulated expression levels of α-SMA and Smad4 by TGF-β1 in LX-2 cells were both suppressed by the recombinant T2 RNase protein. These data suggest that the recombinant T2 RNase protein may be a potential target of therapeutic strategy for the treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Bone marrow stromal cells (BMSCs) up-regulate B cell-activating factor (BAFF) in multiple myeloma. Increasing experimental evidence has shown that microRNAs play a causal role in hematology tumorigenesis. In this study, we characterized the role of miR-202 in regulating the expression of BAFF in BMSCs. It was found that expressions of BAFF mRNA and protein were increased in BMSCs treated with miR-202 inhibitor. The growth rate of miR-202 mimics transfection cells was significantly lower than that of non-transfected cells. The expression of Bcl-2 protein was down-regulated, and Bax protein was up-regulated after miR-202 mimics transfection. Over-expression of miR-202 in BMSCs rendered MM cells more sensitive to bortezomib. More significantly, the regulatory effect of miR-202 could inhibit the activation of NF-κB pathway in BMSCs. These results suggest that miR-202 functions as a modulator that can negatively regulate BAFF by inhibiting MM cell survival, growth, and adhesion in the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

B-cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell-activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl-2 protein was up-regulated, and Bax protein was down-regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p-JNK and p-Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype. However, data on the molecular mechanisms underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory network in myeloma cells that are directly adherent to bone marrow stromal cells (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. Besides, luciferase reporter genes demonstrated direct interaction between miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-ΚB signaling pathway in myeloma cells and the NF-κB P65 was shown to directly bind the miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new insights into the role of tumor microenvironment in the treatment of patients with myeloma. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine the plasma concentrations of acute responding cytokines/chemokines following 9-Gy ionizing radiation in C57BL/6 (radiation tolerant) and C3H/HeN (radiation sensitive) murine strains. Methods and materials: Mice (5/group) received 9-Gy total body irradiation (TBI), and the plasma from each mouse was collected at 6h or 1, 2, 4, or 10days after TBI. A multiplex bead array was used to assess the levels of 32 cytokines/chemokines in plasma to determine their common and strain-specific temporal responses. Results: The plasma levels of five cytokines/chemokines (Axl, FasL, ICAM-1, TARC, and TSLP) were beyond the detectable level. Five (VEGF, IL-2, IL-5, IL-17, and CD30) were unaffected by irradiation in either strain. Temporal patterns were similar in both murine strains for 10 of the cytokines tested, including G-CSF, IL-6, TCA-3, MCP-1, MIP-1γ, KC, CXCL 13, CXCL 16, MDC, and TIMP-1; the other 12 molecules (GM-CSF, IL-3, SCF, IL-1β, IL-4, IL-10, IL-12p70, MIP-1α, Eotaxin, TNF-α, sTNF-R1, and CD40) showed strain-specific response patterns. While a number of cytokines had temporal response patterns following TBI, the strains exhibited quantitatively different results. Conclusions: The levels of 27 of the 32 plasma cytokines measured indicate the following: (1) different cytokine concentrations and temporal patterns in the two strains may partly explain different radiation sensitivities and sequelae following irradiation; (2) many of the cytokines/chemokines exhibit similar temporal responses in the two strains. These responses suggest the potential value of using a panel of cytokine/chemokine temporal patterns for radiation dosimetry. Although radiation doses will be difficult to quantitate due to the large variation in levels and temporal responses exhibited in the two murine strains, serial measurements of cytokines might help identify subjects exposed to radiation. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study was to investigate the function of a proliferation-inducing ligand (APRIL) gene among the metastatic colorectal cancer (CRC) disease. Methods: Cell adhesion, cell migration and invasion behavior were detected after knockdown of APRIL expression in the colon carcinoma cell line, SW480 by RNAi and the rescue experiments were performed with recombinant human APRIL (rhAPRIL) in vitro. Results: This original study indicated that knockdown of APRIL expression strongly inhibited colon carcinoma cell adhesion, cell migration and invasion in vitro. By contrast, reconstitution of APRIL expression with rhAPRIL in these APRILi cells, prominently restores CRC cell migration and invasion. Conclusion: These results strongly suggest that APRIL play an important role in the tumor development of the invasive or migratory behavior of CRC cells and may be a useful therapeutic target in the malignant colon carcinomas. [Copyright &y& Elsevier]

Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats' skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy. [ABSTRACT FROM AUTHOR]

• Designed DNA-peptide probe to capture miR-224. • Converted the miR-224 signal into reporter peptide by a DNA–peptide probe and quantified the reporter peptide by using targeted proteomics. • Determination of sample loading efficiency on beads and hybridization efficiency. • UHPLC-MS/MS analysis was performed by linear regression equation. • Method validation was conducted by the established UHPLC-MS/MS method. MicroRNAs (miRNAs) are known as potential noninvasive biomarkers for cancer diagnosis. Previous studies have been reported that miR-224 is upregulated in hepatocellular carcinoma (HCC) tissues and sera samples. However, current available methods of miRNA detection typically require pre-enrichment, amplification and labeling steps, and mostly they are semi-quantitative. Herein, we developed an isotope dilution mass spectrometry approach to convert the signal of miR-224 into the mass response of a reporter peptide. Specifically, the newly formed DNA-peptide probe was hybridized with miR-224, which was biotinylated and attached to streptavidin agarose in advance. After through trypsinization, solid phase extraction and blow drying, it used a UHPLC/MS/MS-based quasi-targeted proteomics assay for miR-224 quantification and determines the peak area or peak height ratio of labeled and non-labeled analytes to which an isotope label was added to estimate the concentration of the analyte in the sample. Moreover, this method showed good linearity, precision, accuracy and recovery in the calibration range. In addition, it also demonstrated good performance in comparison with qRT-PCR. Taken together, this study may offer a novel direct quantitative method for serum miRNA analysis applied in clinical practice. [ABSTRACT FROM AUTHOR]

• Genome-wide transcriptomic data sets are ideal for biomarker identification. • Long noncoding RNAs that are present at stable levels in serum can serve as biomarkers. • TUG1 levels were significantly elevated in multiple myeloma. • Combined assessment of multiple markers significantly improves diagnostic sensitivity. Long noncoding RNAs (lncRNAs) have increasingly been found to be key mediators of tumor biology and to have potential diagnostic value as biomarkers of particular forms of cancer. TUG1 (taurine-upregulated gene 1) is an lncRNA that has been found to be upregulated in a range of different cancer types, but levels of its expression in the serum of patients with multiple myeloma (MM) are uncertain, as is its diagnostic relevance in such a population. This study therefore explored whether TUG1 levels in patient serum serve as a diagnostic biomarker of MM. We analyzed serum TUG1 levels via quantitative real-time polymerase chain reaction in healthy control and MM patient serum and observed clear TUG1 upregulation in MM patients (p < 0.001). We further found that the levels of TUG1 in patient serum correlated with factors including disease clinical stage, β 2 -microglobulin, total protein, albumin, globulin, and bone injury (p < 0.05), suggesting that this lncRNA may be independently predictive of MM disease stage. We found areas under receiver operating characteristic curves as high as 0.792 (p < 0.001) for TUG1—a value higher than that for either β 2 -microglobulin (0.747) or albumin (0.597)—with the combination of all three biomarkers improving diagnostic specificity and areas under the curve of 96.9% and 0.836, respectively (p < 0.001). Together, our results suggest that serum TUG1 levels may serve as a valuable biomarker that can help to facilitate MM diagnosis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play an important role in the progression of gastric cancer (GC), but its specific regulatory mechanism remains to be further studied. We previously identified that lncRNA B3GALT5-AS1 was upregulated in GC serum. Here, we investigated the functions and molecular mechanisms of B3GALT5-AS1 in GC tumorigenesis. qRT-PCR was used to detect B3GALT5-AS1 expression in GC. EdU, CCK-8, and colony assays were utilized to assess the proliferation ability of B3GAL5-AS1, and transwell, tube formation assay were used to assess the invasion and metastasis ability. Mechanically, FISH and nuclear plasmolysis PCR identified the subcellular localization of B3GALT5-AS1. RIP and CHIP assays were used to analyse the regulation of B3GALT5-AS1 and B3GALT5. We observed that B3GALT5-AS1 was highly expressed in GC, and silencing B3GALT5-AS1 could inhibit the proliferation, invasion, and migratory capacities of GC. Additionally, B3GALT5-AS1 was bound to WDR5 and modulated the expression of B3GALT5 via regulating the ZEB1/β-catenin pathway. High-expressed B3AGLT5-AS1 promoted GC tumorigenesis and regulated B3GALT5 expression via recruiting WDR5. Our study is expected to provide a new idea for clinical diagnosis and treatment., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated., Methods: We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22's influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status., Results: Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC., Conclusion: Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC., (© 2024. The Author(s).)

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers in the world, and early diagnosis can effectively improve patient survival. Here, differentially expressed circIARS genes are screened from the sequencing results, and their molecular characteristics are examined by Sanger sequencing, RNase R assay, agarose gel electrophoresis (AGE), and fluorescence in situ hybridization (FISH). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) is performed to detect the expression level of circIARS. The diagnostic value of the signature is analyzed using a subject operating characteristic (ROC) curve. Moreover, plasma is collected from postsurgical, chemotherapy, and relapse patients to investigate the prognostic value of circIARS in NSCLC. The expression of circIARS is greater in both the plasma and tissues of NSCLC patients than in those of healthy individuals, and could be used to distinguish NSCLC patients from patients with benign pulmonary disease (BPD), small cell lung cancer (SCLC) patients, and healthy individuals. The expression level of circIARS relatively decreases after antitumor therapy, such as chemotherapy, and relatively increases after recurrence. ROC analysis reveals that circIARS has better detection efficiency than traditional markers. In addition, circIARS expression level is strongly correlated with several clinicopathological parameters. Finally, we tentatively predict the downstream miRNAs or RBP that might bind to circIARS. Plasma circIARS is significantly greater in NSCLC patients and has good stability and specificity as a diagnostic marker, which could aid in the adjuvant diagnosis and dynamic monitoring of NSCLC.

Gastric cancer (GC) is one of the most common gastrointestinal tumors. As a newly discovered type of non-coding RNAs, transfer RNA (tRNA)‍-derived small RNAs (tsRNAs) play a dual biological role in cancer. Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC. In this work, we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation, migration, and invasion of GC cells in vitro. The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3' untranslated region (UTR) site of acyl-coenzyme A dehydrogenase short/branched chain ( ACADSB ). In addition, ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells. Next, we used Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis. Finally, we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level, as well as the changes in reactive oxygen species (ROS) levels by flow cytometry. In summary, this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB , thereby promoting GC progression. It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis., Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction., Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC., Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs, which promotes tumor progression to a certain extent. Increasing reports have demonstrated the regulatory role of circular RNAs (circRNAs) in autophagy. Here, we aimed to determine the role of hsa&#95;circ&#95;0009109 in autophagy in gastric cancer (GC)., Methods: The effects of hsa&#95;circ&#95;0009109 on autophagy were examined using quantitative real-time polymerase chain reaction (qPCR), transmission electron microscopy, Western blot, and immunofluorescence. The mechanism of hsa&#95;circ&#95;0009109 regulating the miR-544a-3p/bcl-2 axis was analysed using fluorescence in situ hybridization, dual-luciferase reporter, and rescue experiments., Results: Functional testing indicated that hsa&#95;circ&#95;0009109 was significantly down-expressed in GC tissues and cell lines. A reduction in cytoplasmic-derived hsa&#95;circ&#95;0009109 could promote GC progression by accelerating cell proliferation, enhancing migration and invasion, inhibiting apoptosis, and accelerating the cell cycle progression. Besides, hsa&#95;circ&#95;0009109 was found to exert the effect of an autophagy inhibitor such as 3-Methyladenine (3-MA), which was manifested by the weakening of the immunofluorescence of LC3B and the reduction in autophagy-related proteins after overexpression of hsa&#95;circ&#95;0009109, while increased autophagosomes were observed after interference with hsa&#95;circ&#95;0009109. Subsequently, the crosstalk between hsa&#95;circ&#95;0009109 and miR-544a-3p/bcl-2 was verified using dual-luciferase reporter assay. The autophagy status was altered under the regulation of the hsa&#95;circ&#95;0009109-targeted miR-544a-3p/bcl-2 axis., Conclusions: The hsa&#95;circ&#95;0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis, which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC., Competing Interests: The authors declare that there is no conflict of interests in this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Gastric cancer (GC) is a common malignant digestive system tumor. Since the early symptoms of GC are usually vague and the positive rate of common biomarkers of GC is low, it is of urgent need to find new biomarkers with good sensitivity and specificity to screen and diagnose GC patients. The tRNA-derived small RNAs (tsRNAs) are emerging small noncoding RNAs that play an essential role in cancer progression. In this study, we explored whether novel tsRNAs have the potential to serve as biomarkers for GC. Three tsRNAs significantly upregulated in GC were screened by the tsRFun database. The expression level of tRF-29-R9J8909NF5JP was detected by real-time fluorescence quantitative polymerase chain reaction. Agarose gel electrophoresis and Sanger sequencing were used to verify the characteristics of tRF-29-R9J8909NF5JP. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of tRF-29-R9J8909NF5JP. The χ 2 test was used to analyze the correlation between tRF-29-R9J8909NF5JP expression level and clinicopathological parameters. Kaplan-Meier survival curves were used to analyze the correlation between tRF-29-R9J8909NF5JP expression levels and survival time of GC patients. In this study, the expression level of tRF-29-R9J8909NF5JP was significantly increased in GC tissues. The expression level of tRF-29-R9J8909NF5JP was considerably higher in the serum of GC patients than in the serum of gastritis patients and in the serum of healthy donors, and the expression level of tRF-29-R9J8909NF5JP was significantly decreased in the serum of GC patients after surgery. In addition, the χ 2 test showed that the expression level of tRF-29-R9J8909NF5JP in GC serum was correlated with differentiation grade, T-stage, lymph node metastasis, tumor node metastasis stage, and neurological/vascular invasion. The results of the survival curve showed that the high expression of serum tRF-29-R9J8909NF5JP was associated with a low survival rate. ROC analysis showed that serum tRF-29-R9J8909NF5JP had higher diagnostic efficiency than common GC biomarkers, and the diagnostic efficiency was further improved by combining them. At the end of the study, we predicted the downstream of tRF-29-R9J8909NF5JP. The expression level of tRF-29-R9J8909NF5JP in the serum of GC patients can effectively identify GC patients and has higher efficacy than conventional biomarkers. In addition, serum tRF-29-R9J8909NF5JP can monitor the postoperative condition of GC patients, suggesting that it has the potential to become a biomarker for GC., (© 2023 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Objective: Gastric cancer (GC) has high morbidity and mortality due to inefficient early screening. Therefore, we are searching for more sensitive and specific diagnostic markers for GC. tRNA-derived small RNAs are novel non-coding small RNAs with good abundance and stable presence in body fluids, which may play multiple biological regulatory roles. In this study, we aimed to find a potential biomarker with high accuracy in tRNA-derived small RNAs that can help diagnose GC. Methods: tRF-27-FDXXE6XRK45 was screened as a target molecule by high-throughput sequencing in three pairs of GC tissues. RNA quantitative reverse transcription PCR was conducted to detect the expression levels of tRF-27-FDXXE6XRK45. Agarose gel electrophoresis, Sanger sequencing, cytoplasmic and nuclear RNA isolation assays, gradient dilution experiments, and room temperature and repeated freeze-thaw experiments were used to assess the detection performance of tRF-27-FDXXE6XRK45. Using the chi-square test to analyze the correlation between tRF-27-FDXXE6XRK45 expression levels and clinicopathological parameters. In addition, receiver operating characteristic curves were used to evaluate the diagnostic value of tRF-27-FDXXE6XRK45 in GC. Results: tRF-27-FDXXE6XRK45 expression levels, significantly upregulated in tissues and sera of GC patients and decreased after radical GC surgery, were correlated with the degree of differentiation, depth of tumor infiltration, TNM stage, lymph node metastasis, and nerve/vascular invasion. In comparison with current GC diagnostic markers, tRF-27-FDXXE6XRK45 displayed better efficacy. Conclusions: tRF-27-FDXXE6XRK45, with high diagnostic efficacy, can distinguish GC patients from gastritis patients and healthy donors, suggesting that tRF-27-FDXXE6XRK45 may be a promising candidate as a diagnostic marker for GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Blood count reference intervals are important to diagnose diseases and assess overall health, especially for young children. Although, in 2021, the National Health Commission of the People's Republic of China issued "Reference intervals of blood cell analysis for children (WS/T 779-2021)", these RIs may not suitable for small children all over the country due to racial, lifestyle, and geographical differences. The aim of this study was to establish and validate locally determined hematological reference intervals among young children in Nantong district and compare them with WS/T 779-2021 and American data., Methods: The reference sample consisted of 4,758 apparently healthy small children aged from age 28 days to 3 years according to the EP28-A3c guideline issued by the Clinical and Laboratory Standards Institute (CLSI). Capillary blood samples collected in K2-EDTA anticoagulant tubes analyzed by standard procedures. Statistical analysis was based on the guidelines of the CLSI., Results: Pediatric reference intervals for 18 capillary complete blood count (CCBC) parameters were established for young children. WBC and differentials did not differ by gender in the combined analysis of all data, but showed some variations among different age groups, especially for NE and LYM. RIs of RBC value, MCV, and MCH were established, especially with regard to the difference among different age and gender groups. An overall increasing trend of PLT value was observed in children with no obvious difference between boys and girls. Further validation with 1,136 healthy subjects demonstrated that the verified proportions of our study were within 90.11% - 100%. RIs determined in the present study were more concentrated than WS/T 779-2021, with slight differences in the upper and bottom boundaries., Conclusions: Establishing appropriate region-specific reference intervals for pediatrics is essential. This study offers local reference intervals of CCBC values for young children and could be used as a benchmark for similar populations in the Yangtze River Delta economic region.

With the development of sequencing technology, transfer RNA (tRNA)-derived small RNAs (tsRNAs) have received extensive attention as a new type of small noncoding RNAs. Based on the differences in the cleavage sites of nucleases on tRNAs, tsRNAs can be divided into two categories, tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs), each with specific subcellular localizations. Additionally, the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications. In this review, we first elaborated on the classification and biogenesis of tsRNAs. After summarizing the latest mechanisms of tsRNAs, including transcriptional gene silencing, post-transcriptional gene silencing, nascent RNA silencing, translation regulation, rRNA regulation, and reverse transcription regulation, we explored the representative biological functions of tsRNAs in tumors. Furthermore, this review summarized the clinical value of tsRNAs in cancers, thus providing theoretical support for their potential as novel biomarkers and therapeutic targets., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Glycerophospholipid signal and fatty acid metabolism are closely related to the occurrence and progression of tumours, and metabolic reprogramming caused by hydrolytic enzymes plays an important role in gastric cancer (GC). Here, we performed whole transcriptome sequencing and combined qRT-PCR to screen out the significantly high expression of fatty acid amide hydrolase (FAAH) in GC tissues, which was further verified in both TCGA and Oncomine databases. Functional tests confirmed that FAAH played an oncogene role in GC, and silencing FAAH could delay tumour growth, inhibit tumour metastasis, and promote cell apoptosis both in vitro and in vivo. FAAH-mediated lipid metabolism reprogramming through coordinated regulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signalling and activated the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis to promote GC progression. Luciferase reporter assay and immunofluorescence-fluorescence in situ hybridization (IF-FISH) were applied to validate the interactions of miR-1275/FAAH. Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development., (© 2023. The Author(s).)

Gastric cancer (GC) is one of the most common malignancies in the world, and the search for better markers has become one of the challenges today. It has been found that the L6 superfamily regulates the biological functions of numerous tumors, but transmembrane 4 L six family member 18 (TM4SF18) has been rarely reported. We found that TM4SF18 expression is upregulated in GC tissues and cells, which can be effectively diagnosed and dynamically monitored to assess the prognosis of GC patients. Furthermore, knockdown of TM4SF18 effectively inhibited proliferation, migration, and invasion of GC cells, and affected the epithelial-mesenchymal transition process. TM4SF18 was found to be an independent prognostic factor for GC by univariate and multifactorial Cox analyses as well as by establishing nomogram plots. In addition, in TM4SF18 and immune correlation analysis, TM4SF18 expression levels were found to be negatively correlated with most immune cell marker genes and associated with numerous immune cells and immune pathways, resulting in less benefit from treatment with immune checkpoint inhibitors. In summary, we found that TM4SF18 is a promising GC biomarker that promotes the proliferation, migration, and invasion abilities of GC cells, and is associated with immune response., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Cellular communication between gastric cancer (GC) cells with different metastatic potentials and microenvironments and resultant cancer progression is not fully understood. Circular RNAs (circRNAs) and exosomal circRNAs are known to play extremely important regulatory roles in GC occurrence and progression. Here, we revealed significant differences in coronin-like actin-binding protein 1C (CORO1C) derived circRNA hsa&#95;circ&#95;0000437 between GC and para-cancer tissues. Hsa&#95;circ&#95;0000437 regulated GC cell proliferation, invasion, migration and apoptosis by targeting Ser/Arg-rich splicing factor 3 (SRSF3) and inhibiting programmed cell death 4 (PDCD4). The ectopic expression of hsa&#95;circ&#95;0000437 dramatically promoted tumor growth in nude mice in vivo. Furthermore, both gain-of-function and loss-of-function experiments demonstrated that hsa&#95;circ&#95;0000437 promoted human lymphatic endothelial cells (HLECs) invasion, migration, and tube formation in vitro and also promoted lymphangiogenesis and lymph node metastasis (LNM) in popliteal LNM model in vivo, when it was enriched in GC-secreted exosomes and transferred into HLECs. Mechanistically, exosomal hsa&#95;circ&#95;0000437 induced LNM via HSPA2-ERK signaling pathway independent of VEGF-C. Clinical data showed that exosomal hsa&#95;circ&#95;0000437 was enriched in the serum of GC patients, which was associated with LNM. In summary, these findings highlight the potential role of hsa&#95;circ&#95;0000437 as an outcome biomarker in GC patients with LNM, which may provide a novel target for GC therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

TIPE1 is a gene in the TNFAIP8 family involved in immune regulation and tumorigenesis. Although previous studies demonstrated that TIPE1 might play different roles in different tumors, its expression and role in lymphoma are unclear. Here we observed TIPE1 expression in diffuse large B cell lymphoma (DLBCL). Two microarrays containing 96 tumor tissue specimens were obtained from the Affiliated Hospital of Nantong University biobank. All specimens came from patients with a clear pathological diagnosis of lymphoma, lymphadenitis, breast cancer, or bladder cancer, and we performed immunohistochemical experiments on these tissue specimens. GEPIA and TIMER platforms were used for bioinformatic analyses. We found higher TIPE1 expression in tumor tissues from patients with lymphoma compared with those with lymphadenitis, breast cancer, or bladder cancer. The GEPIA and TIMER analyses revealed that TIPE1 was upregulated in DLBCL tissues but not in invasive breast carcinoma, urothelial bladder carcinoma, or liver hepatocellular carcinoma tissues. TIPE1 expression was irrelevant for pathological stage, overall survival, or DLBCL immune infiltration levels. However, TIPE1 expression was correlated with MKI67 expression in DLBCL. Overall, TIPE1's high expression levels in DLBCL may contribute to tumor growth in DLBCL., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2022 Pei Shen et al., published by De Gruyter.)

Circular RNAs (circRNAs) have become a research hotspot in recent years with their universality, diversity, stability, conservativeness, and spatiotemporal specificity. N 6 -methyladenosine (m 6 A), the most abundant modification in the eukaryotic cells, is engaged in the pathophysiological processes of various diseases. An increasing amount of evidence has suggested that m 6 A modification is common in circRNAs and is associated with their biological functions. This review summarizes the effects of m 6 A modification on circRNAs and their regulation mechanisms in cancers, providing some suggestions of m 6 A-modified circRNAs in cancer therapy., (© 2022. The Author(s).)

Most small non-coding RNAs (sncRNAs) with regulatory functions are encoded by majority sequences in the human genome, and the emergence of high-throughput sequencing technology has greatly expanded our understanding of sncRNAs. sncRNAs are composed of a variety of RNAs, including tRNA-derived small RNA (tsRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNA), etc. While for some, sncRNAs' implication in several pathologies is now well established, the potential involvement of tsRNA, snoRNA, snRNA and piRNA in human diseases is only beginning to emerge. Recently, accumulating pieces of evidence demonstrate that tsRNA, snoRNA, snRNA and piRNA play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer. Abnormal expression of tsRNA, snoRNA, snRNA and piRNA participates in the occurrence and development of tumours through different mechanisms, such as transcriptional inhibition and post-transcriptional regulation. In this review, we describe the research progress in the classification, biogenesis and biological function of tsRNA, snoRNA, snRNA and piRNA. Moreover, we emphasised their dysregulation and mechanism of action in cancer and discussed their potential as diagnostic and prognostic biomarkers or therapeutic targets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs that play indispensable roles in cancers, including colorectal cancer (CRC). However, the role of SNORD1C in CRC is unclear. In the current study, SNORD1C expression was measured in CRC tissues using quantitative real-time PCR. A series of in vivo and in vitro experiments were performed to examine the functional role of SNORD1C in CRC. Quantitative real-time PCR, western blotting, sphere formation assay, and chemotherapy resistance analysis were conducted to illustrate the SNORD1C molecular mechanism. SNORD1C was upregulated in CRC and that high SNORD1C expression was related to poor prognosis. After knocking down SNORD1C in CRC cell lines, cell proliferation, colony formation, cell migration, and invasion were alleviated, while apoptosis was increased. Transcriptional RNA-sequencing analysis revealed that following SNORD1C knockdown, β-catenin was downregulated, as was the transcription factor TCF7, which inhibited the Wnt/β-catenin pathway. Meanwhile, levels of the stem cell-related factors were reduced, diminishing cell stemness and tumorigenesis. Our findings suggest that SNORD1C functions via the Wnt/β-catenin pathway to enhance cancer cell stemness in CRC and could be a predictive biomarker for the prognosis ad aggressiveness of this malignancy. Additionally, targeting SNORD1C may be a novel therapeutic strategy for CRC., (© 2022. The Author(s).)