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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, ACADSBcould 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 ACADSBin GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis. Finally, we verified the correlation between ACADSBand 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.

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_circ_0000437 between GC and para-cancer tissues. Hsa_circ_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_circ_0000437 dramatically promoted tumor growth in nude mice in vivo. Furthermore, both gain-of-function and loss-of-function experiments demonstrated that hsa_circ_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_circ_0000437 induced LNM via HSPA2-ERK signaling pathway independent of VEGF-C. Clinical data showed that exosomal hsa_circ_0000437 was enriched in the serum of GC patients, which was associated with LNM. In summary, these findings highlight the potential role of hsa_circ_0000437 as an outcome biomarker in GC patients with LNM, which may provide a novel target for GC therapy.

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.

ABSTRACTColorectal cancer (CRC) is a common malignancy that has both low 5-year survival and high prevalence. Immunotherapy has achieved impressive progress for treatment of CRC, but still faces huge challenges. Although large tumor suppressor 2 (LATS2) is well accepted to be related to cancer progression, the prognostic potential and immune response role of LATS2 expression in CRC remain unclear. To investigate the value of LATS2 for prognosis and immune infiltration, a retrospective study of 213 CRC patients was carried out. We determined the expression of LATS2 in tumor tissues by immunohistochemistry. The results indicated that LATS2 expression was down-regulated in CRC tissues and clearly related to tumor differentiation (P= 0.002) and TNM stage (P= 0.002). Low LATS2 expression and TNM stage were subsequently identified as significant independent predictors of prognosis in CRC by univariate and multivariate analyses. In Kaplan–Meier survival analyses, CRC patients with elevated LATS2 expression and early TNM stage had better overall survival. We further found that LATS2 was involved in the regulation of immune-related pathways and that its expression was positively related to tumor-infiltrating immune cells by GSEA, TIMER, and ssGSEA analyses. In summary, our data imply that LATS2 may act as a cancer suppressor gene and be correlated with clinical prognosis and immune infiltration in CRC. Thus, LATS2 may be applied as a novel biomarker for predicting clinical outcomes and immune infiltration levels in CRC.

ABSTRACTColorectal cancer (CRC) is the second most incident cancer and third leading cause of cancer-related mortality worldwide. Small nucleolar RNAs (snoRNAs) are small non-coding RNAs located in the nucleoli of cells, and play key roles in multiple cancers. However, the role of serum snoRNAs in CRC remains unknown. We analyzed the expression of the snoRNA SNORD1C in the serum of patients with CRC using quantitative real-time polymerase chain reaction (qRT-PCR) (n = 122). The receiver operating characteristic (ROC) curves were estimated, and the area under the ROC curve (AUC) was calculated. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis of co-expressed genes was performed using the database for annotation, visualization, and integrated discovery (DAVID), and visualized by R language. The results showed that the expression of SNORD1C in patients with CRC (n = 122) was significantly higher than that in normal individuals (n = 50) and patients with benign colorectal disease (n = 33) (P< 0.05). The overexpression of serum SNORD1C was related to poor tissue differentiation and high carcinoembryonic antigen (CEA) levels (P< 0.05). In the ROC curve analysis, SNORD1C serum expression combined with CEA offered better predictive value for the diagnosis of CRC (AUC = 0.838) compared with SNORD1C (AUC = 0.748) or CEA (AUC = 0.715) alone. High expression of SNORD1C was found to be closely associated with prognosis and unfavorable outcomes in patient with CRC. Therefore, serum SNORD1C may be a noninvasive tumor biomarker for diagnosis of CRC.

Aluelements are one of most ubiquitous repetitive sequences in human genome, which were considered as the junk DNA in the past. Aluelements have been found to be associated with human diseases including cancers via events such as amplification, insertion, recombination or RNA editing, which provide a new perspective of oncogenesis at both DNA and RNA levels. Due to the prevalent distribution, Aluelements are widely used as target molecule of liquid biopsy. Alu-based cell-free DNA shows feasible application value in tumour diagnosis, postoperative monitoring and adjuvant therapy. In this review, the special tumourigenesis mechanism of Aluelements in human cancers is discussed, and the application of Aluelements in various tumour liquid biopsy is summarised.

AbstractObjective: We investigated the expression and clinical significance of Cancerous inhibitor of protein phosphatase 2A (CIP2A) in Cutaneous malignant melanoma (CMM).Methods: CIP2A expression was analyzed by immunohistochemistry and western blot. We tested the invasion and migration capability of A375 cells with Matrigel invasion assay, Scratch migration assay and Matrigel migration assay after down-regulating CIP2A expression using siRNA.Results: CIP2A immunostaining level was correlated with Breslow thickness, Clark’s Level and lymphovascular invasion. High-CIP2A expression implied poor survival for patients. Downregulation of CIP2A attenuated metastasis of CMM cells.Conclusions: CIP2A may serve as a novel marker to predict the prognosis for CMM patients.

Much attention has been focused on cell-free DNA (cf-DNA) and its levels in the plasma, serum and body fluids of pregnant women and patients with cancer or autoimmune disease, and those with severe trauma; however, knowledge of its biology and relationship with myocardial infarction (MI) is still at an early stage. This paper introduces general aspects of the nomenclature, structure, function, release mechanisms and methodology of cf-DNA and summarizes the current literature on concentration variation and regulatory mechanisms in MI.

Abstract: APRIL, a member of the TNF superfamily, can induce cell proliferation and is overexpressed in most tumor tissues or cells. Nevertheless, it is still unknown about the effect of decreased levels of APRIL expression on tumor cells. In this study, we analyzed APRIL and HSPG expression in the colon carcinoma cell line, SW480 by Western blot and RT-PCR. And the up-regulation of APRIL and HSPG expression was found in SW480. We also observed that knockdown of APRIL levels in SW480, prominently reversed cell proliferation and partially resulted in senescence phenotypes. Furthermore, cellular senescence due to a decreased level of APRIL expression was associated with engagement of HSPG. Thus, our results suggest that low levels of APRIL play an essential role in cellular senescence via a HSPG-dependent signaling pathway in SW480.