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LncRNA DLX6-AS1 increases the expression of HIF-1? and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p.

ABSTRACT: OBJECTIVE:To investigate the expression of long-chain noncoding growth stasis specific protein 6 antisense RNA1 (lncRNA DLX6-AS1) in nasopharyngeal carcinoma (NPC) tissues and cells, and its regulatory effect on malignant phenotypes of NPC cells. METHODS:The expressions of DLX6-AS1, miR-199a-5p, and HIF-1? mRNA in NPC issues and cells were detected by qRT-PCR. The proliferation, metastasis, and invasion of cells were monitored via MTT and transwell assay. The interactions between DLX6-AS1 and miR-199a-5p, miR-199a-5p and HIF-1? were verified by luciferase activity assay. Western blot was performed to determine the regulatory effect of DLX6-AS1 and miR-199a-5p on HIF-1? protein. RESULTS:The expression of lncRNA DLX6-AS1 was up-regulated in NPC tissues and cells. The proliferation, migration, and invasion of NPC were enhanced by overexpressed DLX6-AS1 but inhibited by DLX6-AS1 knockdown. In addition, DLX6-AS1 can be used as a kind of ceRNA to regulate miR-199a-5p and, thereby modulating the expression of HIF-1?. CONCLUSION:We found that DLX6-AS1 was a cancer-promoting lncRNA to facilitate the progression of NPC, and its underlying mechanism was suppressing miR-199a-5p expression. This study can provide novel clues for the treatment of NPC.

SUBMITTER: Yang B

PROVIDER: S-EPMC6978402 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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LncRNA DLX6-AS1 increases the expression of HIF-1α and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p.

Yang Bin B Jia Lin L Ren Hui H Jin Caibao C Ren Qingrong Q Zhang Haiyuan H Hu Desheng D Zhang Hao H Hu Liu L Xie Tao T

Molecular genetics & genomic medicine 20191129 1

<h4>Objective</h4>To investigate the expression of long-chain noncoding growth stasis specific protein 6 antisense RNA1 (lncRNA DLX6-AS1) in nasopharyngeal carcinoma (NPC) tissues and cells, and its regulatory effect on malignant phenotypes of NPC cells.<h4>Methods</h4>The expressions of DLX6-AS1, miR-199a-5p, and HIF-1α mRNA in NPC issues and cells were detected by qRT-PCR. The proliferation, metastasis, and invasion of cells were monitored via MTT and transwell assay. The interactions between ...[more]

PMID: 31782911

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Project description:BackgroundAccumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC.ResultsUp-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3' un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α).ConclusionsOur data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.

Dataset Information

LncRNA DLX6-AS1 increases the expression of HIF-1? and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p.

Publications

LncRNA DLX6-AS1 increases the expression of HIF-1α and promotes the malignant phenotypes of nasopharyngeal carcinoma cells via targeting MiR-199a-5p.

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