title: Long Noncoding RNA GAS5 Inhibits Tumorigenesis and Enhances Radiosensitivity by Suppressing miR-135b Expression in Non-Small Cell Lung Cancer.
abstract: Growth arrest-specific transcript 5 (GAS5) has been demonstrated to correlate with clinicopathological characteristics and serve as a tumor suppressor in non-small cell lung cancer (NSCLC). However, the underlying mechanism of the competing endogenous RNA (ceRNA) regulatory network involving GAS5 in NSCLC remains to be elucidated. In this study, qRT-PCR results showed that GAS5 was downregulated and miR-135b was upregulated 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 overexpression and miR-135b downregulation significantly suppressed tumorigenesis by repressing cell proliferation and invasion, and enhanced the 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 in vivo. 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.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Xue
authors.forename: Tingting
authors.initials: T
authors.lastname: Ni
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000818:Animals; D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation / Q000528:radiation effects; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D011897:Random Allocation; D014162:Transfection
chemical_list: C561567:GAS5 long non-coding RNA, human; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding