Search

Background: Endometrial cancer (EC) is an intractable gynecological cancer with increasing incidence and mortality worldwide. Accumulating studies indicated that long noncoding RNA nuclear enriched...

Background: Growing evidence demonstrated that long noncoding RNAs (lncRNAs) were involved in the progression of diverse cancers, including breast cancer (BC). Recent studies indicated that lncRNA ...

Background: This study intended to investigate the mechanisms underlying the epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). Materials and Methods: Lung cancer tissue samples were collected from 20 patients with NSCLC (6 EGFR mutation types assigned into 2 categories and 14 EGFR wild types assigned to 4 categories). The samples were subjected to transcriptome sequencing, followed by identification of the differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs) between the mutation and nonmutation groups. Function analysis and microRNA (miRNA) prediction for DEMs were performed. The correlations between long noncoding RNA (lncRNA)/circular RNA (circRNA) and messenger RNA (mRNA) were analyzed. In addition, the targeting lncRNA and circRNA of miRNA were predicted. Finally, competing endogenous RNA (ceRNA) network was constructed, and survival analysis for the mRNAs involved in the network was performed. Results: In total, 323 DEMs, 284 DELs, and 224 DECs were identified between EGFR mutation and nonmutation groups. The DEMs were significantly involved in gene ontology functions related to cilium morphogenesis and assembly. ceRNA networks were constructed based on the DEMs, DELs, DECs, and predicted miRNAs. Survival analysis showed that four genes in the ceRNA network, including ABCA3, ATL2, VAMP1, and APLN, were significantly associated with prognosis. The four genes were involved in several ceRNA pathways, including RP1-191J18/circ_000373/miR-520a-5p/ABCA3, RP5-1014D13/let-7i-5p/ATL2, circ_000373/miR-1293/VAMP1, and RP1-191J18/circ_000373/miR-378a-5p/APLN. Conclusion: EGFR mutations in NSCLC may be associated with cilium dysfunction and complex ceRNA regulatory mechanisms. The key RNAs in the ceRNA network may be used as promising biomarkers for predicting EGFR mutations in NSCLC.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

Long non-coding RNAs (lncRNAs) are a new class of regulatory RNAs that play important roles in disease development and a variety of biological processes. Recent studies have underscored the importance of lncRNAs in the circadian clock system and demonstrated that lncRNAs regulate core clock genes and the core clock machinery in mammals. In this review, we provide an overview of our current understanding of how lncRNAs regulate the circadian clock without coding a protein. We also offer additional insights into the challenges in understanding the functions of lncRNAs and other unresolved questions in the field. We do not cover other regulatory ncRNAs even though they also play important roles; readers are highly encouraged to refer to other excellent reviews on this topic. Accepted version

Background: Pituitary adenoma (PA) is a kind of common primary brain tumor with invasive properties. Although the fact that long noncoding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) exerts oncogenic function in cancer cells and that miR-944 inhibits epithelial-mesenchymal transition (EMT) of cancer cells are well documented, few studies explore the function and mechanism of SNHG6 and miR-944 in invasive pituitary adenoma (IPA). Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of SNHG6 and miR-944 in PA samples. Human PA cell line HP75 was used as a cell model. The biological effects of SNHG6 and miR-944 on HP75 cells were investigated with cell counting kit-8 (CCK-8) assay, Transwell assay, and scratch healing assay in vitro, respectively. Markers of EMT, including E-cadherin and vimentin, were detected by western blot. Interactions between SNHG6 and miR-944, miR-944 and RAB11A were determined by bioinformatics analysis, qRT-PCR, and dual luciferase reporter assay. Results: SNHG6 was significantly upregulated in IPA samples, whereas miR-944 was downregulated. SNHG6 markedly promoted viability, migration, invasion, and EMT of PA cells, whereas miR-944 transfection had the opposite effects. SNHG6 could downregulate miR-944, and there was a negative correlation between SNHG6 expression and miR-944 expression in IPA samples. Besides, it was confirmed that miR-944 could pair with the 3'-untranslated region of RAB11A and repress its expression. Conclusions: This study authenticates that the SNHG6/miR-994/RAB11A axis plays a crucial role in regulating proliferation, migration, invasion, and EMT of IPA cells. SNHG6 and miR-994 can serve as novel valuable therapeutic targets for IPA.

The frequency of human suffering from cancer is increasing annually across the globe. This has fueled numerous investigations aimed at the prevention and cure of various cancers. Long non-coding RNA (lncRNA) are known to play a crucial role in cancer. For instance, cancer susceptibility candidate 11 (CASC11), as one of the long non-coding RNAs, has been reported to be overexpressed in various tumors. This review elucidates the mechanism by which lncRNA CASC11 regulates tumors' biological processes and affirms its value as a therapeutic target for tumors. Through systematic analysis and review of relevant articles in PubMed, we revealed the pathophysiological mechanism of CASC11 on the tumor by regulating the biological processes of tumor such as proliferation, autophagy, apoptosis, thereby promoting tumor metastasis. We also revealed the regulatory pathways of CASC11 in different tumors, for instance by acting on a variety of microRNAs, oncogenic proteins, carcinogens, and transcription factors. Consequently, CASC11 regulates cancer proliferation, apoptosis, and invasion by altering the WNT/β-catenin signaling pathway and epithelial–mesenchymal transition (EMT). Furthermore, CASC11 expression has a high pertinence with clinical prognosis, suggesting that it is a potential marker for malignant tumors or a clinical adjuvant therapy in the future.

Background Long non-coding RNA (lncRNA) is implicated in the progression of multiple cancers. This study aimed to explore the expression characteristics, biological function and molecular mechanism of lncRNA HAGLROS expression in NSCLC. Methods Quantitative real-time polymerase chain reaction (RT-PCR) was adopted to detect HAGLROS expression in NSCLC tissues and normal lung tissues. Survival curve was plotted by Kaplan–Meier method. Gain-of-function and loss-of-function models were respectively established to investigate the biological functions of HAGLROS, miR-100 and SMARCA5. MTT and Transwell assays were carried out to monitor the changes in proliferation, migration and invasion of NSCLC cells. Bioinformatics analysis and dual-luciferase reporter assay were used to verify the binding sites between HAGLROS and miR-100. Western blot was performed to determine the regulatory effects of HAGLROS and miR-100 on SMARCA5 protein expression. Results Up-regulated HAGLROS expression was observed in NSCLC tissues and cell lines. Over-expressed HAGLROS promoted the malignant phenotypes of NSCLC cells; conversely, HAGLROS knockdown repressed the malignant phenotypes of NSCLC cells. HAGLROS repressed miR-100 expression to promote SMARCA5 expression in NSCLC cells, and miR-100 overexpression or SMARCA5 knockdown counteracted the oncogenic functions of HAGLROS. Conclusions These results conclude that HAGLROS is a tumor promoter in NSCLC, and it regulates the malignant phenotypes of NSCLC cells via miR-100/SMARCA5 axis.

Background: Evidence from previous investigations points to a rising trend in the incidence of colorectal cancer (CRC) worldwide. The mortality resulting from this cancer is high. Unlike nonsmall cell lung cancer for which LINC01123 has been investigated, there are few reports on how this long noncoding RNA (lncRNA) regulates CRC. Materials and Methods: The authors evaluated the expression of LINC01123 in CRC tissues by quantitative real-time polymerase chain reaction. Its impact on cancer cell behavior was analyzed with cell counting kit-8 (CCK-8), colony formation, and Transwell invasion assays. To establish the mechanisms of LINC01123 in CRC they carried out RIP and luciferase reporter assays. Results: The results show that LINC01123 expression is abnormally elevated in CRC tissues and cell lines. High LINC01123 expression closely correlates with poor prognosis, advanced TNM stage, and lymph-node metastasis. The authors also show that knockdown of LINC01123 inhibits proliferation and invasion in CRC cells. In mechanism, it is revealed that LINC01123 may function as competitive endogenous RNA (ceRNA) against miR-625-5p to promote LIM and SH3 protein 1 (LASP1) expression. Conclusions: The data indicate that high LINC01123 exerts its oncogenic roles by regulating the miR-625-5p/LASP1 axis in CRC progression.

Metastasis is a major challenge in the treatment of cancer. Exosomes are a class of small extracellular vesicles (EVs) that play critical roles in several human diseases, especially cancer, by transferring information (e.g., DNA, RNA, and protein) via cell-to-cell communication. Numerous recent studies have shown that exosomal long non-coding RNAs (lncRNAs) play crucial regulatory roles in cancer metastasis in the tumor microenvironment by altering the expression of several key signaling pathways and molecules. Due to their specificity and sensitivity, exosomal lncRNAs have potential as novel tumor markers and therapeutic targets in the treatment of cancer metastasis. In this review, we aim to summarize the roles of exosomal lncRNAs in cancer metastasis, the mechanisms underlying their roles, and their potential clinical applications.

Background: Colorectal cancer (CRC), a malignant tumor, has become a highly relevant social problem. Nuclear paraspeckle assembly transcript 1 (NEAT1) was reported as an oncogenic long noncoding RN...

Objective: Vascular smooth muscle cell (VSMC) plasticity plays a critical role in the development of atherosclerosis. Long noncoding RNAs (lncRNAs) are emerging as important regulators in the vessel wall and impact cellular function through diverse interactors. However, the role of lncRNAs in regulating VSMCs plasticity and atherosclerosis remains unclear. Approach and Results: We identified a VSMC-enriched lncRNA cardiac mesoderm enhancer-associated noncoding RNA (CARMN) that is dynamically regulated with progression of atherosclerosis. In both mouse and human atherosclerotic plaques, CARMN colocalized with VSMCs and was expressed in the nucleus. Knockdown of CARMN using antisense oligonucleotides in Ldlr −/− mice significantly reduced atherosclerotic lesion formation by 38% and suppressed VSMCs proliferation by 45% without affecting apoptosis. In vitro CARMN gain- and loss-of-function studies verified effects on VSMC proliferation, migration, and differentiation. TGF-β1 (transforming growth factor-beta) induced CARMN expression in a Smad2/3-dependent manner. CARMN regulated VSMC plasticity independent of the miR143/145 cluster, which is located in close proximity to the CARMN locus. Mechanistically, lncRNA pulldown in combination with mass spectrometry analysis showed that the nuclear-localized CARMN interacted with SRF (serum response factor) through a specific 600–1197 nucleotide domain. CARMN enhanced SRF occupancy on the promoter regions of its downstream VSMC targets. Finally, knockdown of SRF abolished the regulatory role of CARMN in VSMC plasticity. Conclusions: The lncRNA CARMN is a critical regulator of VSMC plasticity and atherosclerosis. These findings highlight the role of a lncRNA in SRF-dependent signaling and provide implications for a range of chronic vascular occlusive disease states.

Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role of GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD. We discovered that overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolism-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1, and GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients. Taken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially may serve as a prognostic marker and therapeutic target in LUAD., Graphical abstract, In this study, we identified lncRNA GAS6-AS1 as a suppressor in tumor progression and glucose metabolism reprogramming of LUAD. GAS6-AS1 exerted its biological role through binding with E2F1 and suppressing E2F1-mediated transcription of glucose transporter GLUT1.

Inappropriately activation of renin-angiotensin-aldosterone system induced renal fibrosis is characterized by partial epithelial-to-mesenchymal transition. Previously, we have indicated that miR-29b-3p in inhibiting partial epithelial-to-mesenchymal transition by negatively regulating extracellular matrix gene expression in the kidney. Despite the critical role of miR-29b-3p in fibrosis, the molecular mechanisms by which miR-29b-3p is regulated under the condition of profibrotic stimuli are largely unknown. Our aim is to search for the long noncoding RNA that mediated sponge regulatory on miR-29b-3p, and whether the long noncoding RNA could be activated by renin-angiotensin-aldosterone system and its consequent effects on renal fibrosis. Bioinformatics analysis predicted that Tug1 might directly bound to miR-29b-3p and function as a competing endogenous RNA. Dual-luciferase reporter assay, fluorescence in situ hybridization, and real-time polymerase chain reaction were performed to indicate that Tug1 interact with miR-29b-3p in a sequence-specific manner. Decreased Tug1 led to an increase in extracellular matrix measured by Western blot, and this effect was enhanced by miR-29b-3p measured by real-time polymerase chain reaction and Western blot, suggesting cross-regulation between the RNAs. Bioinformatics analysis predicted that mineralocorticoid receptor might bind to long noncoding RNA Tug1 . Notably, mineralocorticoid receptor antagonism reduced Tug1 expression in the presence or absence of angiotensin II or aldosterone measured by real-time polymerase chain reaction, and RNA immunoprecipitation assays confirmed that the mineralocorticoid receptor directly bound to Tug1 . Finally, we confirmed that Tug1 expression was enhanced in fibrotic compared with nonfibrotic human renal biopsy samples using RNA-in situ hybridization. Our findings provide novel insights into the molecular mechanism of Ang II–induced renal fibrosis and identify the Tug1 –miR-29b-3p axis as an important target of MR activation.

Introduction Melanoma is a highly aggressive malignant skin tumor as well as the primary reason for skin cancer‐specific deaths. We first identified immune‐related long noncoding RNA (lncRNA) prognostic signature and found potential immunotherapeutic targets for melanoma cancer. Methods RNA‐seq data and clinical features of melanoma samples were obtained from The Cancer Genome Atlas. Samples of melanoma were randomly assigned to the training and testing cohort. The immune‐related lncRNA signature was then obtained via using univariate, LASSO, and multivariate Cox analysis of patients in the training cohort. Eight significant immune‐related lncRNA signature was then subsequently obtained through correlation analysis between immune‐related genes and lncRNAs. The association between risk score and immune cell infiltration was finally assessed using TIMER and CIBERSORT. Results Three hundred and fifty‐six immune‐related lncRNAs were obtained. Among them, eight immune‐related lncRNAs were identified to build a prognostic risk signature model. The model's performance was then confirmed using the Kaplan–Meier curves, risk plots, and time‐dependent receiver‐operating characteristic curves in the training cohort. The risk score was identified and confirmed as an independent prognostic factor through univariate and multivariate Cox regression analyses. These results were further verified in the testing and whole cohorts. CIBERSORT algorithm showed that the infiltration levels of T cells CD8, M1 macrophages, plasma cells, T cells CD4 memory activated, T cells gamma delta, and mast cells activated were significantly lower in the high‐risk group while the infiltration level of macrophages M0 was significantly lower in the low‐risk group. Conclusion The immune‐related lncRNA signature offers prognostic markers and potential immunotherapeutic targets for melanoma., We applied univariate Cox, LASSO, and multivariate Cox regression analysis to identify immune‐related lncRNAs with remarkable prognostic potential and constructed a multiple immune‐related lncRNAs signature to predict melanoma' prognosis. lncRNA signatures of immune‐related offers prognostic markers and potential immunotherapeutic targets for melanoma.

Objective: Long noncoding RNA urothelial carcinoma associated 1 (UCA1) was found to facilitate endometrial cancer cell metastasis, and high UCA1 expression predicted endometrial cancer development ...

Background: Cervical cancer (CC) is the second frequent cancer of women in developing countries. Plentiful studies proved that long noncoding RNA antisense of the tumor suppressor gene WT1 (WT1-AS)...

Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of hepatocellular carcinoma (HCC) and are involved in the stemness regulation of liver cancer stem cells (LCSCs). However, cancer cell stemness-associated lncRNAs and their relevance in prediction of clinical prognosis remain largely unexplored. In this study, through the transcriptome-wide screen, we identified a total of 136 LCSC-associated lncRNAs. We evaluated the prognostic value of these lncRNAs and optimally established an 11-lncRNA (including AC008622.2, AC015908.3, AC020915.2, AC025176.1, AC026356.2, AC099850.3, CYTOR, DDX11-AS1, HTR2A-AS1, LINC02870, and SNHG3) prognostic risk model. Multivariate analysis revealed that the risk score is an independent prognostic predictor for HCC patients, which outperforms the traditional clinical pathological factors. Gene set enrichment analysis suggested that the high-risk score reflects the alteration of pathways involved in cell cycle, oxidative phosphorylation, and metabolism. Furthermore, functional studies on SNHG12, the leading candidate of the risk lncRNAs, revealed that knockdown of SNHG12 reduces the abilities of HCC cells stemness, proliferation, migration, and invasion. In summary, we constructed a prognostic risk model based on 11 LCSC-associated lncRNAs, which might be a promising prognostic predictor for HCC patients and highlight the involvement of lncRNAs in LCSC-associated treatment strategy in clinical practice.

Long non-coding RNAs (lncRNAs) are essential drivers or suppressors in human hepatocellular carcinoma (HCC) by participating in controlling transcription, translation, mRNA stability, and protein degradation protein-protein interaction. TM4SF1-AS1 is recently identified as a tumor-promoting factor in lung cancer. Nevertheless, its function in HCC and related molecular mechanisms remain unknown. Here, our data indicated that either hypoxia or hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (DMOG) induced the upregulation of TM4SF1-AS1 in HCC cells. HIF-1α knockdown rather than HIF-2α silencing remarkably abrogated hypoxia-upregulated TM4SF1-AS1 expression. Furthermore, we confirmed the elevated expression of TM4SF1-AS1 in HCC tissue samples and cell lines. The silencing of TM4SF1-AS1 prominently inhibited the proliferative, migratory, and invasive abilities of HCC cells. TM4SF1-AS1 depletion significantly blocked hypoxia-enhanced Hep3B cell proliferation and mobility. Interfering TM4SF1-AS1 remarkably reduced TM4SF1 mRNA and protein levels in HCC cells. But TM4SF1-AS1 knockdown did not impact the stability of TM4SF1 mRNA. Hypoxia enhanced the expression of TM4SF1 mRNA, which was subsequently decreased by TM4SF1-AS1 knockdown in HCC cells. We confirmed the positive correlation between TM4SF1 mRNA and TM4SF1-AS1 expression in HCC specimens. Finally, TM4SF1 prominently reversed the inhibitory role of TM4SF1-AS1 depletion in Hep3B cells. In summary, hypoxia-responsive TM4SF1-AS1 was overexpressed in human HCC and contributed to the malignant behaviors of tumor cells by enhancing TM4SF1-AS1 expression.

Background: Long noncoding RNAs (lncRNAs) X inactivate-specific transcripts (XIST) have been found to be dysregulated in breast cancer (BC). Nevertheless, the influence and mechanism of XIST on BC progression remain largely undefined. Methods: The expression levels of XIST, miR-362-5p, and ubiquitin-associated protein 1 (UBAP1) mRNA were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion abilities were determined using MTT assay, flow cytometry, and transwell assay, respectively. Targeted relationship between miR-362-5p and XIST or UBAP1 was validated by the dual-luciferase reporter assay. Western blot was performed to evaluate UBAP1 protein level. Xenograft mice model was established for the investigation of XIST in tumor growth. Results: The authors' data indicated that XIST and UBAP1 were downregulated in BC tissues and cells. XIST overexpression weakened BC cell proliferation, migration, invasion, and facilitated the apoptosis, and XIST silencing exerted opposite effect. Mechanistically, XIST directly interacted with miR-362-5p and miR-362-5p mediated the regulatory effects of XIST overexpression on BC cell malignant behaviors. UBAP1 was a direct target of miR-362-5p. MiR-362-5p exerted its regulatory effects on BC cell behaviors by UBAP1. Moreover, XIST modulated UBAP1 expression through acting a competing endogenous RNA of miR-362-5p. XIST overexpression mediated antiproliferation, antimigration, anti-invasion, and proapoptosis effects were abated by the restored expression of UBAP1 in BC cells. Furthermore, the upregulation of XIST hindered tumor growth in vivo. Conclusion: The current study suggested that XIST overexpression hampered BC cell progression in vitro and in vivo at least partially by targeting the miR-362-5p/UBAP1 axis, illuminating XIST as a promising therapeutic agent for BC management.

Purpose. Hepatocellular carcinoma (HCC) accounts for approximately ninety percent of primary liver cancer. This study attempted to investigate the effects of the long noncoding RNA MIR100HG (MIR100HG) in HCC and the underlying molecular mechanism. Materials and Methods. qRT-PCR was implemented to analyze the expression of MIR100HG, microRNA-146b-5p (miR-146b-5p), and Chromobox 6 (CBX6). The correlation between MIR100HG and clinicopathological features of HCC patients was assessed. Additionally, the effects of MIR100HG knockdown on HCC cell viability, migration, and invasion were explored. The interactions among MIR100HG, miR-146b-5p, and CBX6 were confirmed. Furthermore, rescue experiments were conducted to investigate whether MIR100HG knockdown modulates HCC cell behaviors through modulating the miR-146b-5p/CBX6 axis. Results. The expression of MIR100HG and CBX6 was enhanced, while miR-146b-5p was inhibited in HCC cells. High MIR100HG expression was positively associated with the TNM tumor stage and Edmondson-Steiner grading in HCC patients. MIR100HG knockdown considerably reduced the HCC cell viability, migration, and invasion. In addition, MIR100HG directly targeted miR-146b-5p, and miR-146b-5p directly targeted CBX6 in HCC cells. Moreover, miR-146b-5p suppression or CBX6 elevation evidently rescued the suppressed viability, migration, and invasion of HCC cells caused by MIR100HG knockdown. Conclusions. Knockdown of MIR100HG inhibited the viability, migration, and invasion of HCC cells by targeting the miR-146b-5p/CBX6 axis, offering a potential therapeutic target for HCC therapy.

Purpose To identify the potential genes in human trabecular meshwork (TM) related to primary open-angle glaucoma (POAG). Methods First, long noncoding RNA (LncRNA) and mRNA expression profiles in TM samples from 4 control subjects and 4 POAG patients were accessed by microarray analyses. Then, twenty lncRNAs were validated by real-time quantitative PCR in the same samples from microarray analyses. Finally, eight highly expressed lncRNAs were further tested by real-time quantitative PCR in TM from 8 normal controls and 19 POAG patients. Expression data were normalized and analyzed using the R software. Pathway analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results A total of 2179 lncRNAs and 923 mRNAs in the TM of POAG patients were significantly upregulated, and 3111 lncRNAs and 887 mRNAs were significantly downregulated. ENST00000552367, ENST00000582505, ENST00000609130, NR_029395, NR_038379, and ENST00000586949 expression levels were significantly higher in the TM from a different cohort of POAG patient than normal controls. Conclusion ENST00000552367, ENST00000582505, ENST000006091- 30, NR_029395, NR_038379, and ENST00000586949 may play essential roles in the development of POAG.

This study primarily focused on the effect of the long noncoding RNA (lncRNA) PVT1/miR186/KLF5 axis on the occurrence and progression of cholangiocarcinoma (CCA). miR186 was found both in the lncRNA PVT1 targeting miRNAs and KLF5 targeting miRNAs using bioinformatic analysis. The expression of lncRNA PVT1 and KLF5 in the TFK-1, QBC939, and HuCCT1 cell lines and normal biliary epithelial HIBEpiC cells was detected by RT-qPCR. The significance of lncRNA PVT1 and KLF5 on cell proliferation was analyzed using the MTT assay and clone formation assay in lncRNA PVT1 and KLF5 silencing HuCCT1 cell lines and lncRNA PVT1and KLF5 overexpressing TFK-1 and QBC939 cell lines, respectively. The potential role of lncRNA PVT1 and KLF5 in cell migration was detected using the transwell invasion assay in CCA cell lines and tumor formation assay. Additionally, lncRNA PVT1 and KLF5 were proved to be highly expressed in CCA tissues and cell lines. Silencing and overexpressing of lncRNA PVT1 or KLF5 markedly inhibited or increased the cell proliferation and cell invasion in CCA cell lines, respectively. Silencing and overexpressing of lncRNA PVT1 significantly inhibited and increased the expression of KLF5 in CCA cell lines, respectively. Silencing of lncRNA PVT1 increased the expression of miR186, and silencing of miR186 increased the expression of KLF5 in CCA cell lines. Cotransfection of lncRNA PVT1 and miR186 increased the expression of KLF5 compared with controls. Overall, these results demonstrated that the lncRNA PVT1/miR186/KLF5 axis might exert a key role in the occurrence and progression of CCA, and this axis might provide a new target for treating CCA.

Breast cancer is the most common cancer in women with the highest mortality among this gender. Despite treatment strategies including surgery, hormone therapy and targeted therapy have recently advanced, innovative biomarkers are needed for the early detection, treatment and prognosis. An increasing number of non-coding RNAs (ncRNAs) have shown great potential as crucial players in different stages of the breast cancer tumorigenesis, influencing cell death, metabolism, epithelial-mesenchymal transition (EMT), metastasis and drug resistance. Long non-coding RNAs (lncRNAs), specifically, are a class of RNA transcripts with a length greater than 200 nucleotides, which have also been shown to exerts oncogenic or tumour suppressive roles in the pathogenesis of breast cancer. LncRNAs are implicated in different molecular mechanisms by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. Here, we aim to briefly discuss the latest existing body of knowledge regarding the key functions and the molecular mechanisms of some of the most relevant lncRNAs in the pathogenesis, treatment and prognosis of breast cancer.

Background Long non-coding RNAs (lncRNAs) are important epigenetic regulators, which play critical roles in diverse physiological and pathological processes. However, the regulatory mechanism of lncRNAs in lung carcinogenesis remains elusive. Here, we characterized a novel oncogenic lncRNA, designated as Lung Cancer Associated Transcript 3 (LCAT3). Methods We predicted and validated LCAT3 by analyzing RNA-sequencing (RNA-seq) data of lung cancer tissues from TCGA. Methylated RNA immunoprecipitation was performed to assess m6A modification on LCAT3. The LCAT3-FUBP1-MYC axis was assessed by dual-luciferase reporter, RNA immunoprecipitation and Chromatin immunoprecipitation assays. Signaling pathways altered by LCAT3 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT3 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro. Results LCAT3 was found to be up-regulated in lung adenocarcinomas (LUAD), and its over-expression was associated with the poor prognosis of LUAD patients. LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. Biologically, loss-of-function assays revealed that LCAT3 knockdown significantly suppressed lung cancer cell proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. LCAT3 knockdown induced cell cycle arrest at the G1 phase. Mechanistically, LCAT3 recruited Far Upstream Element Binding Protein 1 (FUBP1) to the MYC far-upstream element (FUSE) sequence, thereby activating MYC transcription to promote proliferation, survival, invasion and metastasis of lung cancer cells. Conclusions Taken together, we identified and characterized LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-MYC axis as a potential therapeutic target for LUAD.

Metastatic neuroendocrine prostate cancer (NEPC) is a highly aggressive disease, whose incidence is rising. Long noncoding RNAs (lncRNAs) represent a large family of disease‐ and tissue‐specific transcripts, most of which are still functionally uncharacterized. Thus, we set out to identify the highly conserved lncRNAs that play a central role in NEPC pathogenesis. To this end, we performed transcriptomic analyses of donor‐matched patient‐derived xenograft models (PDXs) with immunohistologic features of prostate adenocarcinoma (AR+/PSA+) or NEPC (AR−/SYN+/CHGA+) and through differential expression analyses identified lncRNAs that were upregulated upon neuroendocrine transdifferentiation. These genes were prioritized for functional assessment based on the level of conservation in vertebrates. Here, LINC00261 emerged as the top gene with over 3229‐fold upregulation in NEPC. Consistently, LINC00261 expression was significantly upregulated in NEPC specimens in multiple patient cohorts. Knockdown of LINC00261 in PC‐3 cells dramatically attenuated its proliferative and metastatic abilities, which are explained by parallel downregulation of CBX2 and FOXA2 through distinct molecular mechanisms. In the cell cytoplasm, LINC00261 binds to and sequesters miR‐8485 from targeting the CBX2 mRNA, while inside the nucleus, LINC00261 functions as a transcriptional scaffold to induce SMAD‐driven expression of the FOXA2 gene. For the first time, these results demonstrate hyperactivation of the LINC00261‐CBX2‐FOXA2 axes in NEPC to drive proliferation and metastasis, and that LINC00261 may be utilized as a therapeutic target and a biomarker for this incurable disease., Neuroendocrine prostate cancer (NEPC) is a highly aggressive disease with high incidence of metastasis. Here, we identified LINC00261 among the top upregulated transcripts in NEPC. Inside the nucleus, LINC00261 promoted anchorage‐independent growth and metastatic gene programs by recruiting the SMAD2/3 transcriptional machinery to FOXA2 cis‐regulatory elements. Cytoplasmic LINC00261 blocked the binding of miR‐8485 to CBX2 and induced a CBX2‐driven proliferative gene program. Our study demonstrates the role of LINC00261‐CBX2‐FOXA2 axis in proliferation and metastasis of NEPC.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration., Long noncoding RNAs (lncRNAs) are known to regulate the DNA damage response (DDR), however their role in the brain is less well studied. Here, the authors demonstrate a neuron-specific role for Brain Specific DNA-damage Related lncRNA1 (BS-DRL1) and show BS-DRL1 modulates DDR by interacting with HMGB1 in a cell-type specific manner.

Long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) has been reported to be implicated in chemoresistance. However, the potential mechanism of HULC in paclitaxel (PTX)-resistant ovarian cancer (OC) remains undefined. The expression of RNAs and proteins was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assay. The PTX resistance and apoptotic rate were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Furthermore, the interaction between miR-137 and HULC or integrin beta-8 (ITGB8) was predicted by miRcode and starBase v2.0 and then verified by dual luciferase reporter and RNA pull-down assays. In addition, the xenograft mice model was established to explore the effects of HULC in vivo. HULC was significantly upregulated and miR-137 was downregulated in PTX-resistant OC tissues and cells. Also, the HULC depletion suppressed tumor growth and PTX resistance in PTX-treated mice. miR-137 was verified as a target of HULC and directly targeted ITGB8. And HULC knockdown downregulated ITGB8 expression by targeting miR-137. miR-137 inhibitor or ITGB8 overexpression mitigated the suppressive impacts of HULC knockdown on PTX resistance. Collectively, HULC modulated ITGB8 expression to promote PTX resistance of OC by sponging miR-137.

Background Epigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood. This study investigated the role of long noncoding RNA (lncRNA) lnc-STYK1-2 in tumorigenesis in cancerous bladder cells. Methods Differential lncRNA and mRNA profiles were characterized by high-throughput RNA sequencing combined with validation via quantitative PCR. Bladder cancer cell proliferation was assessed through MTS, and bladder cancer cell migration and invasion were assessed through a Transwell system. The in vivo tumorigenesis of bladder cancer cells was evaluated using the cancer cell line-based xenograft model. The dual-luciferase reporter assay verified the association of miR-146b-5p with lnc-STYK1-2 and the target gene. Protein abundances and phosphorylation were detected by Western blotting. Results Alterations in lncRNA profiles, including decreased lnc-STYK1-2 expression, were detected in bladder cancer tissues compared with adjacent noncancerous tissues. lnc-STYK1-2 silencing effectively promoted proliferation, migration, and invasion in two bladder cancer cell lines, 5637 and T24, and their tumorigenesis in nude mice. lnc-STYK1-2 siRNA promoted miR-146b-5p and reduced ITGA2 expression in bladder cancer cells. Moreover, miR-146b-5p suppressed ITGA2 expression in bladder cancer cells through direct association. Also, lnc-STYK1-2 directly associated with miR-146b-5p. Finally, miR-146b-5p inhibitors abrogated the alterations in bladder cell functions, ITGA2 expression, and phosphorylation of AKT, STAT3, and P65 proteins in 5637 and T24 cells induced by lnc-STYK1-2 silencing. Conclusion lnc-STYK1-2 inhibited bladder cancer cell proliferation, migration, and tumorigenesis by targeting miR-146b-5p to regulate ITGA2 expression and AKT/STAT3/NF-kB signaling.

The role of the long noncoding RNA CCAT1 NC_000008.10:g.128220661C > T (rs67085638) in the development of colon cancer has been reported. Therefore, we assessed the prevalence of rs67085638 in patients with gastric cancer (GC). We also evaluated the effect of rs67085638 on B-cell-specific Moloney leukaemia virus insertion site 1 (BMI1) transcripts in primary GC and counterpart histopathologically confirmed disease-free margin tissue. Using high-resolution melting analysis, we evaluated rs67085638 frequency in patients with the GC genotype (n = 214) and controls (n = 502) in a Polish Caucasian population. qRT-PCR was used to determine BMI1 transcripts. We observed the trend of rs67085638 association in all patients with GC (ptrend = 0.028), a strong risk of the GC genotype in male (ptrend = 0.035) but not female (ptrend = 0.747) patients, and the association with non-cardia GC (ptrend = 0.041), tumour stages T3 (ptrend = 0.014) and T4 (ptrend = 0.032), differentiation grading G3 (ptrend = 0.009), lymph node metastasis stage N3 (ptrend = 0.0005) and metastasis stage M0 (ptrend = 0.027). We found that significantly increased BMI1 transcripts were associated with the primary GC genotype classified as grade G3 (p = 0.011) and as lymph node metastasis N3 (p = 0.010) and counterpart marginal tissues (p = 0.026, p = 0.040, respectively) from carriers of the T/T versus C/C genotypes. rs67085638 may contribute to increased BMI1 transcripts and the progression and rapid growth of GC.

Long non-coding RNAs (lncRNAs) are known to competitively bind with microRNAs (miRNAs) to participate in human cancers. We aim to explore the role of non-coding RNA activated by DNA damage (NORAD) binding to miR-323a-3p in breast cancer (BC) with the involvement of pumilio RNA-binding family member 1 (PUM1)/eukaryotic initiation factor 2 (eIF2) axis. Expression of NORAD, miR-323a-3p and PUM1 in tissues and cell lines was detected, and the correlation between NORAD expression and clinicopathological features of BC patients was analyzed. The screened cell line was respectively transfected with altered NORAD or miR-323a-3p to reveal their roles in viability, migration, invasion and apoptosis of BC cells in vitro. The tumor growth in vivo was observed in nude mice. The binding relationships among NORAD, miR-323a-3p and PUM1 were analyzed, and the regulatory role of NORAD and miR-323a-3p in the eIF2 signaling pathway was assessed. NORAD and PUM1 were upregulated and miR-323a-3p was downregulated in BC. High NORAD expression indicated a poor prognosis of BC patients. NORAD inhibition or miR-323a-3p elevation inhibited malignant behaviors of BC cells. The in vivo assay revealed that NORAD inhibition or miR-323a-3p elevation inhibited tumor growth as well. MiR-323a-3p inhibition reversed the role of NORAD knockdown in the biological functions of BC cells while silencing PUM1 reversed the influence of NORAD overexpression on BC cells. NORAD bound with miR-323a-3p and miR-323a-3p targeted PUM1. NORAD and miR-323a-3p functioned through the PUM1/eIF2 axis. NORAD inhibition or miR-323a-3p elevation suppresses the development of BC through the PUM1/eIF2 axis.

PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro, viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro, GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML.

Long non-coding RNAs (lncRNAs) have been shown to impact important biological functions such as proliferation, survival, and genomic stability. To analyze radiation-induced lncRNA expression in human tumors, we irradiated prostate cancer cells with a single dose of 10 Gy or a multifractionated radiotherapeutic regimen of 10 fractions with a dose of 1 Gy (10 × 1 Gy) during 5 days. We found a stable upregulation of the lncRNA LINC00261 and LINC00665 at 2 months after radiotherapy that was more pronounced after single-dose irradiation. Analysis of the The Cancer Genome Atlas (TCGA) and The Atlas of Non-coding RNAs in Cancer (TANRIC) databases showed that high expression of these two lncRNAs may be a potential negative prognostic marker for overall survival of prostate cancer patients. Knockdown of LINC00261 and LINC00665 in long-term survivors decreased survival after re-irradiation and affected DNA double-strand break repair. Mechanistically, both lncRNAs showed an interdependent expression and regulated expression of the DNA repair proteins CtIP (RBBP8) and XPC as well as the microRNA miR-329. Identifying long-term tumor adaptation mechanisms can lead to the discovery of new molecular targets, in effect opening up new research directions and improving multimodal radiation oncologic treatment., Graphical Abstract, Irradiation can induce long-term effects on the expression of long non-coding RNAs in cancer cells, resulting in tumor adaptation, enhanced tumor cell survival, and radiation resistance, which can be targeted to increase radiosensitivity and treatment efficacy.

Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) exert crucial modulation roles in the biological behaviors of multiple malignancies. Nonetheless, the specific function of lncRNA LINC00284 in papillary thyroid cancer (PTC) remains not fully understood. The objective of this research was to explore the influence of LINC00284 in PTC and elucidate its potential mechanism. The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO) datasets were used to analyze LINC00284 expression differences in thyroid cancer and normal samples, followed by the verification of qRT-PCR in our own PTC and adjacent non-tumor tissues. The impacts of LINC00284 on PTC cell growth were detected in vitro via CCK-8, colony formation, EdU assays, and in vivo via a xenograft tumor model. Bioinformatics analyses and biological experiments were conducted to illuminate the molecular mechanism. We found that LINC00284 expression was remarkably increased in PTC tissues and its overexpression was closely correlated with larger tumor size. In addition, silencing LINC00284 could effectively attenuate PTC cell proliferation, induce apoptosis and G1 arrest in vitro, as well as suppress tumorigenesis in mouse xenografts. Mechanistic investigations showed that LINC00284 acted as a competing endogenous RNA (ceRNA) for miR-3127-5p, thus resulting in the disinhibition of its endogenous target E2F7. In short, our findings indicated that LINC00284–miR-3127-5p–E2F7 axis exerted oncogenic properties in PTC and may offer a new promising target for the diagnosis and therapy of PTC.

Cervical cancer (CC) is a common malignancy in women. Long noncoding RNA LINC00899 plays a role in cancer, but its effects in CC are unknown. Our experiment aims to investigate the specific effects of LINC00899 in CC. LINC00899 was lowly expressed in CC tissues and cells, and overexpressed LINC0089 inhibited the viability, proliferation, migration, and invasion of CC cells, whereas silencing of LINC00899 had the opposite effect. There is a targeting relationship between LINC0089 and miR-944. It was found that miR-944 could competitively bind with LINC00899, and LINC00899 in turn, could downregulate expression of miR-944. Moreover, estrogen receptor 1 (ESR1) was the target gene of miR-944. Overexpressed miR-944 inhibited ESR1 expression, yet enhanced the migration and invasion of CC cells and promoted the expression levels of N-cadherin and Vimentin while inhibiting the expression of E-cadherin. However, overexpressed ESR1 reversed the effect of miR-944 overexpression on CC cells. LINC00899/miR-944/ESR1 axis regulates the proliferation, migration, and invasion of CC cells by regulating the expression levels of related proteins.

Diabetic retinopathy (DR) is a severe diabetes-induced eye disease, in which its pathological phenomena basically include abnormal proliferation, migration, and angiogenesis of microvascular endothelial cells in the retina. Long non-coding RNAs (lncRNAs) have been proven to be important regulators in various biological processes, but their participation in DR remains largely undiscovered. In the present study, we aimed to unveil the role of lncRNA small nucleolar RNA host gene 16 (SNHG16) in regulating the functions of human retinal microvascular endothelial cells (hRMECs) under a high-glucose (HG) condition. We found that SNHG16 expression was significantly upregulated in hRMECs treated with HG. Functionally, SNHG16 could facilitate hRMEC proliferation, migration, and angiogenesis. Moreover, SNHG16 was associated with nuclear factor κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Mechanistically, SNHG16 could promote hRMEC dysfunction by sequestering microRNA (miR)-146a-5p and miR-7-5p to act as a competing endogenous RNA (ceRNA) with interleukin-1 receptor-associated kinase 1 (IRAK1) and insulin receptor substrate 1 (IRS1). In conclusion, our results illustrated the potential role of SNHG16 in facilitating hRMEC dysfunction under HG treatment, providing a novel approach for DR therapy., Graphical Abstract, Upregulation of long non-coding RNA SNHG16 promotes diabetes-related retinal microvascular endothelial cell dysfunction. SNHG16 interacts with miR-146a-5p and miR-7-5p to upregulate IRAK1 and IRS1. SNHG16 exerts functions via activating NF-κB and PI3K/AKT pathways.

DNA proficient mismatch repair colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long noncoding RNAs (lncRNAs) in pMMR CC carcinogenesis. In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and coexpression network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values compared to serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. In conclusion, several lncRNAs play various roles in the adenoma-carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.

Background BRE-AS1 is a recently identified tumor suppressor in non-small cell lung cancer. It role in other human diseases remains elusive. Methods Differential expression of BRE-AS1 in with triple-negative breast cancer (TNBC) patients (n = 74, patient group) and healthy volunteers (n = 58, control group) was studied with RT-qPCR. The direct interaction between BRE-AS1 and premature microRNA-21 (miR-21) was assessed by RNA pull-down assay. The interactions among BRE-AS1, miR-21 and PTEN were evaluated by overexpression assays. CCK-8 assay and Transwell assay were used to evaluate cell behaviors. Results BRE-AS1 was downregulated in TNBC, while miR-21 was highly expressed in TNBC. Low expression levels of lncRNA BRE-AS1 and high expression levels of miR-21 were significantly correlated with unfavorable survival outcomes. BRE-AS1 and miRNA-21 were inversely correlated across TNBC samples, not control samples. BRE-AS1 decreased miR-21 expression and increased PTEN expression while miR-21showed no role in BRE-AS1 expression. RNA pull-down assay illustrated that BRE-AS1 may sponge premature miR-21 to suppress it maturation. Overexpression of BRE-AS1 decreased cell behaviors, while overexpression of miR-21 promoted cell behaviors. MiR-21 suppressed the role of BRE-AS1 in cancer cell behaviors. Conclusion Therefore, BRE-AS1 may inhibit TNBC by downregulating miR-21.

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs or miRs), and genes are emerging players in cancer progression. In the present study, we explored the roles and interactions of oncogenic lncRNA small nucleolar RNA host gene 1 (SNHG1), miR-376, forkhead box protein K1 (FOXK1), and Snail in hepatocellular carcinoma (HCC). Expression of SNHG1, miR-376, and FOXK1 in HCC was characterized in clinical HCC tissues of 75 patients with HCC. The interactions between SNHG1 and miR-376 and between miR-376 and FOXK1 were predicted and confirmed by dual-luciferase reporter gene and RNA immunoprecipitation assays. Overexpression and knockdown experiments were performed in HCC cells to examine the effects of the SNHG1/miR-376/FOXK1/Snail axis on viability, apoptosis, invasiveness, and migrating abilities. Their effects on tumor growth and metastasis were validated in nude mouse models. SNHG1 and FOXK1 were upregulated, and miR-376a was downregulated in HCC. SNHG1 knockdown contributed to suppression of HCC cell viability, invasion, and migration properties and promotion of apoptosis. SNHG1 could competitively bind to miR-376a to upregulate its target gene FOXK1, which upregulated Snail. SNHG1 knockdown delayed cancer progression both in vitro and in vivo by upregulating miR-376a and downregulating FOXK1 and Snail. SNHG1 knockdown exerts anti-tumor activity in HCC, suggesting a therapeutic target., Graphical Abstract, SNHG1 is highly expressed in HCC. SNHG1 competitively binds to miR-376a and inhibits the expression of miR-376a, thereby promoting FOXK1 and Snail expression, leading to reduction of HCC cell proliferative, migrating, and invasive properties, and promotes cell apoptosis and promotion of tumor growth and metastasis in HCC.

Background There is evidence that long non-coding RNA (lncRNA) is related to genetic stability. However, the complex biological functions of these lncRNAs are unclear. Method TCGA - KIRC lncRNAs expression matrix and somatic mutation information data were obtained from TCGA database. “GSVA” package was applied to evaluate the genomic related pathway in each samples. GO and KEGG analysis were performed to show the biological function of lncRNAs-mRNAs. “Survival” package was applied to determine the prognostic significance of lncRNAs. Multivariate Cox proportional hazard regression analysis was applied to conduct lncRNA prognosis model. Results In the present study, we applied computational biology to identify genome-related long noncoding RNA and identified 26 novel genomic instability-associated lncRNAs in clear cell renal cell carcinoma. We identified a genome instability-derived six lncRNA-based gene signature that significantly divided clear renal cell samples into high- and low-risk groups. We validated it in test cohorts. To further elucidate the role of the six lncRNAs in the model’s genome stability, we performed a gene set variation analysis (GSVA) on the matrix. We performed Pearson correlation analysis between the GSVA scores of genomic stability-related pathways and lncRNA. It was determined that LINC00460 and LINC01234 could be used as critical factors in this study. They may influence the genome stability of clear cell carcinoma by participating in mediating critical targets in the base excision repair pathway, the DNA replication pathway, homologous recombination, mismatch repair pathway, and the P53 signaling pathway. Conclusion subsections These data suggest that LINC00460 and LINC01234 are crucial for the stability of the clear cell renal cell carcinoma genome.

Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB. MALAT1 was upregulated in RB tissues and cells, and it served as a competing endogenous RNA (ceRNA) and inhibited miRNA-655-3p (miR-655-3p) expression, which eventually regulated the expression of miR-655-3p downstream target ATPase Family AAA Domain Containing 2 (ATAD2). The level of ATAD2 significantly increased, while that of miR-655-3p remarkably decreased in RB tissues and cells. MALAT1 depletion inhibited cell proliferation, metastasis, and epithelial–mesenchymal transition (EMT), but promoted apoptosis in vitro and blocked xenograft tumor growth in vivo. MALAT1 exerted its oncogenic functions in RB by regulating miR-655-3p/ATAD2 axis.

Pulmonary arterial hypertension (PAH) is a chronic progressive cardiovascular disease characterized by vascular remodeling and leading to right‐heart failure. The purpose of this research was to further study the pathogenesis of PAH and to detect potential prognostic signatures. Differentially expressed genes (DEGs) selected from GSE38267 were mostly enriched in inflammation‐related pathways, suggesting inflammation may be involved in the occurrence and development of PAH. Through the prediction and verification of related miRNAs and long noncoding RNAs using online databases and Gene Expression Omnibus (GEO) datasets, CCR7 and its related molecules, including hsa‐let‐7e‐5p and SNHG12, were identified as possible targets. The expression levels of CCR7, hsa‐let‐7e‐5p and SNHG12 were then verified by quantitative RT‐PCR in vivo and in vitro. Further study showed that silencing of SNHG12 decreased the expression of CCR7 under hypoxia treatment in vitro. Dual‐luciferase reporter assays were used to verify the relationship between hsa‐let‐7e‐5p and SNHG12. Collectively, our research reveals that a long noncoding RNA–miRNA–mRNA interaction network may be involved in the pathogenesis of PAH and suggests SNHG12, hsa‐let‐7e‐5p and CCR7 as potential biomarkers for PAH., Pulmonary arterial hypertension (PAH) is a chronic progressive cardiovascular disease characterized by vascular remodeling, leading to right‐heart failure. In this study, we detected the pathways and potential molecules related to PAH through bioinformatics and experiments in vivo and in vitro. We identified SNHG12, hsa‐let‐7e‐5p and CCR7 as potential biomarkers for PAH.

BackgroundOsteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells.MethodsRelative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p.ResultsRelative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells.ConclusionsOverexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.

Emerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignant tumors in dermatology, and its incidence is increasing year by year. Long non-coding RNAs (lncRNAs) play vital roles in the processes of various malignant tumors. This study aimed to evaluate the expression of long non-coding RNA PICSAR and investigate whether serum PICSAR could serve as a biomarker for the diagnosis and prognosis of cSCC. The expression level of PICSAR was measured using quantitative Real-Time PCR. The diagnostic value of PICSAR was evaluated by receiver operating characteristic (ROC) analysis. Survival curves were established using the Kaplan-Meier method, and the log-rank test was used to compare differences between the two curves. Prognostic value of PICSAR was confirmed by Cox regression analysis. The expression of PICSAR was upregulated in serum of cSCC patients and tumor tissues of patients. Additionally, serum PICSAR expression had relatively high diagnostic accuracy for the screening of cSCC. Moreover, PICSAR expression was correlated with tumor size, grade of differentiation and TNM stages, and significantly increased in cSCC patients with poor tumor differentiation and cSCC patients with III-IV TNM stage. Furthermore, patients with high PICSAR expression had lower overall survival than the patients with low PICSAR expression, and PICSAR expression was an independent prognostic factors for cSCC patients. The results of this study indicated that PICSAR was upregulated in cSCC patients and tumor tissues and might serve as a non-invasive biomarker for the diagnosis and prognosis of cSCC patients.

In this study, we investigated the expression and functions of long noncoding RNAs (LncRNAs) of LINC01518 in an in vitro model of TGF-β1-treated human Tenon capsule fibroblast (HTF) cells. qRT-PCR was used to examine LINC01518 expression in in situ human glaucoma tissues, and in vitro HTF cells treated with TGF-β1. Lentivirus-mediated LINC01518 knockdown was performed in HTF cells to investigate its effect on TGF-β1-induced cell proliferation, migration and autophagy signaling pathway. The potential ceRNA candidate of LINC01518, hsa-miR-216b-5p, was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-216b-5p was also knocked down in LINC01518-downregulated HTF cells to investigate the function of this lncRNA-miRNA epigenetic axis in TGF-β1-treated HTF cells. LINC01518 was upregulated in human glaucoma tissues and cultured HTF cells. LINC01518 downregulation significantly suppressed TGF-β1-induced cell proliferation, migration and autophagy signaling pathway in HTF cells. Hsa-miR-216b-5p was confirmed to be a ceRNA target of LINC01518. Knocking down hsa-miR-216b-5p reversed the suppressing effects of LINC01518 downregulation in TGF-β1-treated HTF cells. Our study demonstrated that LINC01518 is a functional factor in regulating proliferation and migration in TGF-β1-treated HTF cells, and hsa-miR-216b -5p may also be involved. Targeting the epigenetic axis of LINC01518/hsa-miR-216b-5p may provide new insight into the pathological development of human glaucoma.

The functions of long noncoding RNAs (lncRNAs) have been widely investigated in human cancers, including gastric cancer (GC). The purpose of this study was to elucidate the role of lncRNA HCG11 in GC. In this study, mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis. The proliferation ability of GC cells was examined by (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide) MTT assays. The invasion and migration abilities of GC cells were evaluated by Transwell assays. The binding sites between miR-942-5p and HCG11/BRMS1 were confirmed by dual-luciferase reporter assays. Results showed that LncRNA HCG11 was downregulated in GC cells. Functionally, overexpression of HCG11 inhibited GC cell proliferation, migration, and invasion. In addition, lncRNA HCG11 was found to act as a molecular sponge of miR-942-5p. Furthermore, miR-942-5p promoted GC progression by suppressing lncRNA HCG11 expression. Besides that, BRMS1 was confirmed as a direct target of miR-942-5p. More importantly, breast cancer metastasis suppressor 1 (BRMS1) inhibited GC progression by upregulating lncRNA HCG11 and downregulating miR-942-5p. In conclusion, LncRNA HCG11 inhibited cell proliferation, migration, and invasion in GC by sponging miR-942-5p and upregulating BRMS1.

The long non‐coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS‐CoV‐2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID‐19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs‐PCGs of BALF samples established by three trans‐acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS‐CoV‐2 genome, suggesting the major regulatory role of these lncRNAs during the SARS‐CoV‐2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS‐CoV‐2 infected cells. (c) In contrast to the 3′ part of the SARS‐CoV‐2 genome, the 5′ part can interact with many human lncRNAs. Therefore, the mRNA‐based vaccines will not show any side effects because of the off‐label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non‐coding RNA‐based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.

Long noncoding RNAs (lncRNA) have been shown to play critical regulatory roles in the onset and progression of human cancers. However, the functions of a large proportion of lncRNAs are still unexplored. Here we describe a novel lncRNA, CTD-2245E15.3, that promotes lung tumorigenesis by regulating the anabolic enzymes acetyl-CoA carboxylase 1 (ACC1, encoded by the ACACA gene) and pyruvate carboxylase (PC). Differentially expressed lncRNAs between non–small cell lung cancer (NSCLC) and paired adjacent nontumor tissues were identified by a microarray and validated using quantitative real-time polymerase chain reaction. CTD-2245E15.3 was significantly upregulated in NSCLC and was mainly located in the cytoplasm. Knockdown of CTD-2245E15.3 by specific antisense oligonucleotides suppressed cell growth in vitro and in vivo, largely due to cell-cycle arrest and induction of apoptosis. Overexpression of CTD-2245E15.3 in an orthotopic model of lung cancer led to a significant increase in total tumor burden. CTD-2245E15.3 exerted its oncogenic function by binding ACC1 and PC, which are key anabolic factors for biomolecule synthesis in rapidly proliferating tumor cells. Knockdown of CTD-2245E15.3 increased phosphorylation of ACC1 at an inhibitory site for enzymatic activity and promoted PC degradation via ubiquitination. Supplements of palmitate or oxaloacetate, products of ACC1 and PC, alleviated the suppression of cell growth caused by loss of CTD-2245E15.3. These findings reveal the important role of CTD-2245E15.3 as an oncogenic lncRNA in the anabolic process for tumor growth. Significance: These findings demonstrate a novel lncRNA CTD-2245E15.3 that binds and positively regulates anabolic enzymes ACC1 and PC to promote tumor growth.