LncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC6781974 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of non-small cell lung cancer (NSCLC). However, how lncRNA deleted in lymphocytic leukaemia 2 (DLEU2) contributes to NSCLC remains undocumented. The clinical significance of lncRNA DLEU2 and miR-30a-5p expression in NSCLC was analysed by using fluorescence in situ hybridization and TCGA cohorts. Gain- and loss-of-function experiments as well as a NSCLC tumour model were executed to determine the role of lncRNA DLEU2 in NSCLC. DLEU2-sponged miR-30a-5p was verified by luciferase reporter, and RIP assays. Herein, the expression of lncRNA DLEU2 was elevated in NSCLC tissues, and its high expression or low expression of miR-30a-5p acted as an independent prognostic factor of poor survival and tumour recurrence in NSCLC. Silencing of lncRNA DLEU2 repressed the tumorigenesis and invasive potential of NSCLC, whereas re-expression of lncRNA DLEU2 showed the opposite effects. Furthermore, lncRNA DLEU2 harboured a negative correlation with miR-30a-5p expression in NSCLC tissues and acted as a sponge of miR-30a-5p, which reversed the tumour-promoting effects of lncRNA DLEU2 by targeting putative homeodomain transcription factor 2 in NSCLC. Altogether, lncRNA DLEU2 promoted the tumorigenesis and invasion of NSCLC by sponging miR-30a-5p.
| S-EPMC6933340 | biostudies-literature
Project description:Despite the rapidly identified numbers of lncRNA in humans, exploration of the molecular mechanisms of lncRNA is lagging, because the molecular mechanisms of lncRNA can be various and complex in different conditions. In this study, we found a new molecular mechanism for a versatile molecule, MIR22HG. MIR22HG is an lncRNA that contributes to the initiation and progression of many human cancers, including hepatocellular carcinoma (HCC). We report that MIR22HG was downregulated in 120 HCC samples compared with adjacent nontumor liver tissues. More interestingly, decreased expression of MIR22HG in HCC could predict poor prognosis of HCC patients. Knockdown of MIR22HG promoted the growth, migration and invasion of HCC cells. In exploring the molecular mechanism of MIR22HG, we found that MIR22HG functioned as a tumor suppressor in hepatocellular carcinomas, in part through serving as a competing endogenous RNA to modulate the miRNA-10a-5p level. Moreover, NCOR2 was verified to act as the downstream target gene of MIR22HG/miR-10a-5p. In addition, the MIR22HG/miRNA-10a-5p/NCOR2 axis inhibited the activation of the Wnt/β-catenin pathway. Together, our results demonstrated that MIR22HG inhibited HCC progression in part through the miR-10a-5p/NCOR2 signaling axis and might act as a new prognostic biomarker for HCC patients.
| S-EPMC6398879 | biostudies-other
Project description:Long non-coding RNAs (lncRNAs) widely participate in ESCC development and progression; however, the prognostic factors and therapeutic strategies implicated in ESCC development and progression remain to be under investigation. The purpose of the current study was to explore whether WDFY3-AS2 may be a potential prognostic factor and investigate its biological functions in ESCC. Here, WDFY3-AS2 was frequently down-regulated in ESCC tissues and cells, and its expression was correlated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Moreover, WDFY3-AS2 down-regulation significantly promoted cell proliferation and invasion, whereas WDFY3-AS2 up-regulation markedly suppressed cell proliferation and invasion in ESCC EC9706 and TE1 cells, coupled with EMT phenotype alterations. WDFY3-AS2 functioned as a competing endogenous RNA (ceRNA) for sponging miR-2355-5p, further resulted in the up-regulation of its target gene SOCS2, followed by suppression of JAK2/Stat5 signalling pathway, to suppress ESCC cell proliferation and invasion in EC9706 and TE1 cells. These findings suggest that WDFY3-AS2 may participate in ESCC development and progression, and may be a novel prognostic factor for ESCC patients, and thus targeting WDFY3-AS2/miR-2355-5p/SOCS2 signalling axis may be a novel therapeutic strategy for ESCC patients.
| S-EPMC7348145 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) have been identified as potential prognostic tools and therapeutic biomarkers for a variety of human cancers. However, the functional roles and underlying mechanisms of key lncRNAs affecting laryngeal squamous cell carcinomas (LSCCs) are largely unknown. Here, we adopted a novel subpathway strategy based on the lncRNA-mRNA profiles from the Cancer Genome Atlas (TCGA) database and identified the lncRNA deleted in lymphocytic leukemia 2 (DLEU2) as an oncogene in the pathogenesis of LSCCs. We found that DLEU2 was significantly upregulated and predicted poor clinical outcomes in LSCC patients. In addition, ectopic overexpression of DLEU2 promoted the proliferation and migration of LSCC cells both in vivo and in vitro. Mechanistically, DLEU2 served as a competing endogenous RNA to regulate PIK3CD expression by sponging miR-30c-5p and subsequently activated the Akt signaling pathway. As a target gene of DLEU2, PIK3CD was also upregulated and could predict a poor prognosis in LSCC patients. In conclusion, we found that the novel LSCC-related gene DLEU2 enhances the malignant properties of LSCCs via the miR-30c-5p/PIK3CD/Akt axis. DLEU2 and its targeted miR-30c-5p/PIK3CD/Akt axis may represent valuable prognostic biomarkers and therapeutic targets for LSCCs.
| S-EPMC7303144 | biostudies-literature
Project description:Background:Non-small cell lung cancer (NSCLC) is the most deadly cancer worldwide. LncRNA KCNQ1OT1 has been reported to be involved in the progression of various tumors, including NSCLC. However, the precise mechanism of KCNQ1OT1 in NSCLC requires further investigation. Methods:The expression levels of KCNQ1OT1, miR-129-5p and JAG1 were detected by qRT-PCR or western blot. Kaplan-Meier survival analysis was used to assess the correlation between KCNQ1OT1 expression and the overall survival of NSCLC patients. CCK-8 assay was used to measure cell viability. Cell migration and invasion were detected by transwell assay. The targets of KCNQ1OT1 and miR-129-5p were predicted by bioinformatics, which was confirmed by dual-luciferase reporter assay or pull-down assay. Results:KCNQ1OT1 expression was significantly enhanced, while miR-129-5p expression was dramatically reduced in NSCLC tissues and cells. Higher KCNQ1OT1 shortened overall survival and was positively associated with tumor stage and lymph node metastasis. KCNQ1OT1 knockdown inhibited proliferation, migration and invasion of NSCLC cells. Inhibition of miR-129-5p attenuated the inhibition of NSCLC cell viability, migration and invasion induced by KCNQ1OT1 knockdown. In addition, JAG1 was confirmed as a target of miR-129-5p. Knockdown of JAG1 reversed the effects of miR-129-5p knockdown on NSCLC progression. KCNQ1OT1 regulated JAG1 expression by sponging miR-129-5p in NSCLC cells. Conclusion:KCNQ1OT1 induced proliferation, migration and invasion of NSCLC cells by sponging miR-129-5p and regulating JAG1 expression, indicating that KCNQ1OT1 was a therapeutic target for NSCLC.
| S-EPMC7195752 | biostudies-literature
Project description:BackgroundOral cancer (OC) is common cancer in the world. Long noncoding RNAs (lncRNAs) have been shown to be involved in cancer regulation, including oral cancer (OC). The aim of this study was to investigate the role of lncRNA deleted in lymphocytic leukemia 2 (DLEU2) in oral cancer.MethodThe Gene Expression Omnibus database was used to analyze differentially expressed lncRNA/microRNA (miRNA, miR)/mRNA. The expression levels of DLEU2, miR-30a-5p, and RAP1B in OC cells were detected by RT-qPCR. Dual-luciferase was used to analyze the binding of lncRNA/miRNA/mRNA. Cell Counting Kit-8 was used to measure cell proliferation. Transwell assay was used to inspect cell migration and invasion abilities. Western blot was used to detect MAPK pathway-related protein levels.ResultOur research shows that, in contrast to miR-30a-5p, DLEU2 or RAP1B was upregulated in OC cells, and high expression of DLEU2 or RAP1B was associated with poorer overall survival. Inhibiting the expression of DLEU2 slowed the proliferation and reduced the ability of migration and invasion of Tca8113 and CAL-27 cells. miR-30a-5p was predicted to interact with DLEU2 or RAP1B by bioinformatics, and dual-luciferase analysis confirmed this interaction. Notably, si-DLEU2 suppressed RAP1B expression and protein level, and after overexpression of RAP1B in OC cells, reversal of suppressed DLEU2 expression was observed. Furthermore, the inhibitory effect of si-DLEU2 on MAPK signaling was reversed by overexpression of RAP1B. Therefore, si-DLEU2 regulates MAPK signaling through the miR-30a-5p/RAP1B axis and inhibits OC development.ConclusionDLEU2 contributed to proliferation, migration and invasion via miR-30a-5p/RAP1B axis to regulate MAPK signaling pathway in OC cells.
| S-EPMC9581637 | biostudies-literature
Project description:Accumulating evidence indicates that m6A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m6A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m6A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo, whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m6A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m6A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.
| S-EPMC10467386 | biostudies-literature
Project description:DLEU2 has been proved to act as an oncogene in a variety of cancers, but its role in cardiovascular diseases is dearth of research. Thus, this study mainly discussed the effect and possible mechanism of DLEU2 on platelet-derived growth factor-BB (PDGF-BB)-triggered vascular smooth muscle cell (VSMC) injury. To obtain authentic results, the expressions of target genes in atherosclerosis serum were determined by reverse transcription quantitative PCR (RT-qPCR) and the protein levels were evaluated by Western blot. PDGF-BB was used to simply simulate the biological characteristics of VSMCs in vitro. The effect of DLEU2 on the biological behavior of PDGF-BB-induced VSMCs was analyzed by gain- and loss-of-function assays. Bioinformatics analysis, dual luciferase reporter assay, and Pearson correlation method were conducted to determine the relationship between target genes. The role of DLEU2/miR-212-5p/ YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) axis in PDGF-BB-induced VSMCs was verified by rescue experiments. As a result, DLEU2 and YWHAZ were up-regulated, and miR-212-5p was down-regulated in atherosclerosis serum. Overexpressed DLEU2 facilitated the biological behavior of PDGF-BB-induced VSMCs, whilst siDLEU2 did the opposite. Moreover, overexpressed DLEU2 promoted proliferating cell nuclear antigen (PCNA) expression but repressed α-smooth muscle actin (α-SMA) and Calponin expressions, while it also enhanced YWHAZ expression via suppressing miR-212-5p. MiR-212-5p mimic and siYWHAZ reversed the effects of overexpressed DLEU2 on above biological characteristics and protein expressions in PDGF-BB-induced VSMCs, while the regulatory effect of miR-212-5p mimic was partially offset by overexpressed YWHAZ. Collectively, DLEU2 modulates PDGF-BB-induced VSMC injury via miR-212-5p/YWHAZ axis in atherosclerosis.
| S-EPMC9467609 | biostudies-literature
Project description:The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both in vitro and in vivo. In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.
| S-EPMC7097916 | biostudies-literature
Project description:Colorectal cancer (CRC) is a prevalent malignancy worldwide. The development of genome sequencing technology has allowed the discovery that epigenetic regulation might play a critical role in CRC tumorigenesis. In the present study, we found that the long noncoding RNA (lncRNA) SNHG4 was dramatically increased in CRC tissue samples and cell lines based on both publicly available and experimental data. SNHG4 knockdown suppressed the viability and colony formation capacity of CRC cells. The expression of CDK1 was considerably increased in CRC tissue samples and cells and had a positive correlation with the expression of SNHG4 in CRC. SNHG4 silencing not only caused S phase cell cycle arrest but also significantly downregulated the CDK1, cyclin B1, and cyclin A2 protein levels in CRC cells. miR-590-3p simultaneously bound to SNHG4 and CDK1. miR-590-3p functioned to inhibit CDK1 expression. miR-590-3p overexpression exerted the same effects on the CRC cell phenotype as SNHG4 knockdown. The effects of si-SNHG4 on CRC cells were significantly reversed by anti-miR-590-3p, indicating that SNHG4 relieved the miR-590-3p-induced inhibition of CDK1 by acting as a competing endogenous RNA (ceRNA). In vivo, SNHG4 silencing inhibited subcutaneously transplanted tumor growth and decreased cell cycle marker levels, whereas miR-590-3p inhibition exerted the opposite effects. The in vivo effects of SNHG4 silencing were also reversed by miR-590-3p inhibition. The SNHG4/miR-590-3p/CDK1 axis influences the cell cycle to modulate CRC cell proliferation and subcutaneously transplanted tumor growth. Further application of this axis still requires analysis using more animal models and clinical investigations.
| S-EPMC8064176 | biostudies-literature