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LncRNA GAS5 Inhibits Tumorigenesis and Enhances Radiosensitivity By Suppressing miR-135b Expression in Non-Small Cell Lung Cancer.

Research paper by Yingbo Y Xue, Tingting T Ni, Ying Y Jiang, Yong Y Li

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Oncology research



Abstract

GAS5 has been demonstrated to be correlated with clinicopathological characteristics and serve as a tumor suppressor innon small cell lung cancer (NSCLC). However, the underlying mechanism of competing endogenous RNA (ceRNA) regulatory network involving GAS5 in NSCLC remains to be elucidated. In this study, qRT-PCR results showed that GAS5 was down-regulated and miR-135b was up-regulated in NSCLC tissues and cells. The expressions of GAS5 and miR-135b changed inversely in response to irradiation. Gain of function experiments revealed that GAS5 overexpresion and miR-135b downregulation significantly suppressed tumorigenesis by repressing cell proliferation, invasion and enhanced radiosensitivity of NSCLC cells by reducing colony formation rates. Luciferase reporter assay confirmed that GAS5 could directly target miR-135b and negatively regulate its expression. Moreover, rescue experiments demonstrated that miR-135b upregulation markedly abolished GAS5 overexpression-induced tumorigenesis inhibition and radiosensitivity improvement. Furthermore, Xenograft model analysis validated that GAS5 overexpression suppressed tumor growth and improved radiosensitivity of NSCLC cells <em>in vivo</em>. Taken together, GAS5 inhibits tumorigenesis and enhances radiosensitivity by suppressing miR-135b expression in NSCLC cells, deepening our understanding of the mechanism of miRNA-lncRNA interaction and providing a novel therapeutic strategy for NSCLC.