LncRNA LINC01535 promotes colorectal cancer development and chemoresistance by sponging miR-761.
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ABSTRACT:
SUBMITTER: Zhao C
PROVIDER: S-EPMC8112154 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance.MethodsCell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes.ResultsSNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1.ConclusionSNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.
| S-EPMC6734319 | biostudies-literature
Project description:ObjectivesLncRNA nuclear-enriched abundant transcript 1 (NEAT1) participates in the development and progression of multiple malignancies. However, the molecular mechanism by which NEAT1 contributes to colorectal cancer (CRC) remains unclear.MethodsThe association between lncRNA NEAT1 expression and clinicopathological characteristics and prognosis in patients with CRC was analysed by TCGA RNA-sequencing data. MTT, colony formation, flow cytometry, transwell assays and a xenograft tumour model were used to assess the functions of NEAT1. Bioinformatics and spearman correlation analysis were used to identify the NEAT1-specific binding with miRNAs, and luciferase gene report and RIP assays were performed to confirm the interaction between miR-193a-3p (miR-193a) and NEAT1 in CRC cells.ResultsUpregulation of NEAT1 expression was significantly correlated with TNM stage, poor survival and tumour recurrence in patients with CRC, and acted as an independent prognostic factor for tumour recurrence. Knockdown of NEAT1 suppressed cell proliferation, colony formation abilities and invasive potential and induced cell apoptosis, but overexpression of NEAT1 reversed these effects. Furthermore, NEAT1 was confirmed to act as a sponge of miR-193a, and knockdown of NEAT1 attenuated miR-193a inhibitor-induced tumour promoting effects and L17RD expression in CRC cells. miR-193a harboured negative correlation with NEAT1 and IL17RD expression in CRC specimens. In vivo experiment further validated the inhibitory effects of NEAT1 knockdown on xenograft tumour growth.ConclusionOur findings demonstrate that lncRNA NEAT1 acts as an oncogenic role in CRC cells by sponging miR-193a and may represent a potential marker for CRC patients.
| S-EPMC6430453 | biostudies-literature
Project description:BackgroundPrevious studies have shown that long noncoding RNA (lncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this lncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1).MethodsThirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo.ResultsLINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis.ConclusionKnockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR-490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.
| S-EPMC7158027 | biostudies-literature
Project description:Increasing research has demonstrated that lncRNAs participate in the development of multiple cancer types. However, the role of TTN‑AS1 in endometrial cancer (EC) remains unknown. The present study aimed to explore the function of titin‑antisense RNA1 (TTN‑AS1) in EC progression and the underlying mechanisms. qRT‑PCR was performed to assess the TTN‑AS1 expression patterns in EC tissues and cell lines. Loss of function experiments were carried out to estimate the effects of TTN‑AS1 on EC cell proliferation, migration and invasion. To reveal the underlying mechanisms, informatics tools were used to predict the targets. Rescue experiments were performed to investigate the TTN‑AS1‑regulated miR‑376a‑3p/pumilio homolog 2 (PUM2) axis involved. The results of the present study revealed that TTN‑AS1 was highly expressed in both EC tissues and cell lines, and TTN‑AS1 knockdown inhibited EC cell proliferation, migration and invasion. With respect to the mechanisms, miR‑376a‑3p was revealed to be targeted by TTN‑AS1, and reversed the effects on EC development induced by TTN‑AS1. In addition, PUM2 was positively regulated by TTN‑AS1, and miR‑376a‑3p mediated the regulation between them. Furtherly, in vivo experiments confirmed the results. Collectively, TTN‑AS1 enhanced EC cell proliferation and metastasis by targeting the miR‑376a‑3p/PUM2 axis, which may shed light on EC diagnosis and treatment.
| S-EPMC7448418 | biostudies-literature
Project description:Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.74-6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.
| S-EPMC5856798 | biostudies-literature
Project description:BackgroundAbnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets.MethodsWe analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer (CRC). The functions of small nucleolar RNA host gene 6 (SNHG6) were investigated through in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, wound healing assay, transwell assay, and xenograft model). The mechanism of action of SNHG6 was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay, and RNA immunoprecipitation assay.ResultsWe identified aberrantly expressed lncRNAs in CRC. We found that elevated SNHG6 expression was associated with poor prognosis and CRC progression. We also demonstrated that the high SNHG6 expression was partly due to DNA copy number gains and SP1 induction. Functional studies showed that SNHG6 promoted CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, we found that SNHG6 expressed predominantly in the cytoplasm. SNHG6 could interact with miR-26a, miR-26b, and miR-214 and regulate their common target EZH2.ConclusionsOur study elucidated that SNHG6 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.
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Project description:GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual-luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR-137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.
| S-EPMC8173206 | biostudies-literature
Project description:Liver cancer is a malignant tumor that occurs in the liver and can be divided into primary and secondary liver cancer. Long non?coding RNA (lncRNA) breast cancer anti?estrogen resistance 4 (BCAR4) has been demonstrated to promote the development of various types of cancer. However, the function of lncRNA BCAR4 in liver cancer remains unclear. In the present study, the expression of lncRNA BCAR4 was notably elevated in liver cancer compared with adjacent non?tumor tissues. Functional in vitro assays demonstrated that knockdown of lncRNA BCAR4 inhibited the proliferation, migration and invasion of Huh?7 cells. In addition, lncRNA BCAR4 was demonstrated to directly bind to microRNA (miR)?1261, and miR?1261 expression negatively correlated with the expression of lncRNA BCAR4. Through bioinformatics analysis, lncRNA BCAR4 was predicted to target anaphase?promoting complex subunit 11 (ANAPC11) through miR?1261. In addition, the results demonstrated that lncRNA BCAR4 increased the expression of ANAPC11 by inhibiting miR?1261 expression. Consistently, overexpression of ANAPC11 or inhibition of miR?1261 significantly rescued liver cancer cell proliferation induced by knockdown of lncRNA BCAR4. Collectively, the results of the present study demonstrated that lncRNA BCAR4 may promote liver cancer development by directly binding to miR?1261 and targeting ANAPC11.
| S-EPMC7255484 | biostudies-literature
Project description:Ovarian cancer is a kind of cancer from the female genital tract; the molecular mechanism still needs to be explored. lncRNA plays a vital role in tumorigenesis and development. Our aim was to identify oncogenic lncRNAs in ovarian cancer and explore the potential molecular mechanism. SNHG15 was initially identified by using GEO datasets (GSE135886 and GSE119054) and validated by tumor tissues and the cell line, identifying that SNHG15 was upregulated in ovarian cancer. Besides, high SNHG15 indicated poor prognosis in ovarian cancer. Furthermore, knockdown SNHG15 suppresses ovarian cancer proliferation and promotes apoptosis. Mechanistically, SNHG15 promotes proliferation through upregulated CDK6 via sponging miR-370-3p. Taken together, our findings emphasize the important role of SNHG15 in ovarian cancer, suggesting that SNHG15 may be a promising target for ovarian cancer.
| S-EPMC8560251 | biostudies-literature
Project description:Colorectal cancer (CRC) is currently one of the commonest tumors and the main reason for cancer-related deaths worldwide. It has been reported that long non-coding RNAs (lncRNAs) act as important indicators and regulators in various cancers. There is an urgent need to explore new lncRNA biomarkers in CRC, as well as their functions and molecular mechanisms. NALT1 has been implicated in the occurrence of gastric cancer (GC). However, the detailed function and mechanism of NALT1 in CRC progress have not been reported. In this study, RT-qPCR was conducted to detect the expression of NALT1 in 76 CRC patients ranging from stages I through IV. To assess the biological function of NALT1, loss- and gain-of-function experiments were conducted both in vivo and in vitro. Moreover, RNA-seq, bioinformatics analysis, RNA pulldown assay, dual-luciferase reporter, Ago2-RIP, quantitative PCR, Western blot assays, and rescue experiments were performed to reveal the molecular mechanisms of competitive endogenous RNAs (ceRNAs). It was observed that high expression of NALT1 was markedly correlated with advanced cancer stage in the clinic. Functionally, NALT1 downregulation inhibited cell proliferation, migration and invasion, whereas NALT1 overexpression exhibited an opposite trend both in vivo and in vitro. Bioinformatics analysis, RNA pulldown, Ago2-RIP, and luciferase reporter assays showed that miRNA-574-5p was a target of NALT1. Additionally, dual-luciferase reporter assays, Ago2-RIP, and rescue experiments indicated that miRNA-574-5p could target the PEG10 gene directly. Our results suggested that NALT1 promoted CRC proliferation and migration by sponging miRNA-574-5p to upregulate PEG10 expression, and implied that NALT1 might act as a promising biomarker and therapeutic target for CRC.
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