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MicroRNA-301b-3p Downregulation Underlies a Novel Inhibitory Role of Long Non-coding RNA MBNL1-AS1 in Non-small Cell Lung Cancer

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Publisher Biomed Central
Date 2019 May 23
PMID 31113460
Citations 25
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Abstract

Background: Non-small cell lung cancer (NSCLC) is the second most prevalent cause of cancer-related fatality. Long non-coding RNAs (lncRNAs) have been observed to exercise functions in NSCLC. Here, the current study aimed to explore the potential mechanism of lncRNA MBNL1-AS1 in NSCLC.

Methods: Microarray analysis was performed to screen the differentially expressed lncRNA associated with NSCLC and its potential mechanism. The lncRNA MBNL1-AS1 expression was quantified in 56 paired NSCLC and adjacent normal tissue samples. In an attempt to outline the function of lncRNA MBNL1-AS1 in NSCLC and to identify the interaction among lncRNA MBNL1-AS1, microRNA-301b-3p (miR-301b-3p) and TGFBR2, ectopic expression, depletion, and reporter assay experiments were conducted to detect CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC.

Results: Initially, the intersection among lncRNA MBNL1-AS1, miR-301b-3p, and TGFBR2 was observed in NSCLC. While a poor expression of lncRNA MBNL1-AS1 and TGFBR2, along with a high expression of miR-301b-3p was observed in NSCLC tissues. A demonstration of lncRNA MBNL1-AS1 restoration significantly decreased CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 functioned as a sponge of miR-301b-3p, which inverted the inhibitory role of lncRNA MBNL1-AS1 in CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 positively regulated TGFBR2 which was a target gene of miR-301b-3p. At last, upregulated lncRNA MBNL1-AS1 or depleted miR-301b-3p suppressed the xenograft tumor formation in vivo.

Conclusion: Collectively, the present study suggests an inhibitory role of lncRNA MBNL1-AS1 in CSC drug resistance of NSCLC by upregulating miR-301b-3p-targeted TGFBR2.

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