Open AccessLong non‐coding RNA OIP5‐AS1 promotes proliferation of lung cancer cells and leads to poor prognosis by targeting miR‐378a‐3p
Author(s) -
Wang Maolong,
Sun Xiao,
Yang Yuling,
Jiao Wenjie
Publication year - 2018
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12767
Subject(s) - cyclin dependent kinase 6 , downregulation and upregulation , cell growth , cancer research , long non coding rna , biology , antisense rna , microrna , lung cancer , in vivo , rna , microbiology and biotechnology , cell , medicine , gene , cell cycle , cyclin d1 , pathology , biochemistry
Background The antisense of the OIP5‐AS1 gene is a long non‐coding RNA (lncRNA) that is reported to be upregulated and promotes cell proliferation in multiple human cancers; however, its function in lung cancer is unknown. We investigated the regulatory function and underlying mechanisms of OIP5‐AS1 in lung cancer. Methods OIP5‐AS1 and microRNA (miR)‐378a‐3p expression were assayed by quantitative real‐time PCR, and proliferation‐related protein expression was measured by Western blotting. Cell viability was detected using methyl thiazolyl tetrazolium assay. Luciferase reporter assay and RNA immunoprecipitation were used to detect the direct regulation of miR‐378a‐3p by OIP5‐AS1. Nude mice were used to test the function of OIP5‐AS1 in vivo. Results OIP5‐AS1 was highly expressed in lung cancer tissues and was correlated with tumor size and tumor growth speed. OIP5‐AS1 overexpression increased lung cancer cell proliferation in vitro. Further investigation revealed that OIP5‐AS1 functions as a competing endogenous RNA of miR‐378a‐3p. MiR‐378a‐3p overexpression inhibited cell proliferation and caused proliferation‐associated proteins CDK4 and CDK6 to decrease in A549 cells. Overexpression of wild type OIP5‐AS1 led to strong CDK4 and CDK6 expression; however, these two proteins did not change when mutated OIP5‐AS1 was upregulated. Finally, in vivo assay showed that the speed of tumor growth was increased and decreased when OIP5‐AS1 was upregulated and downregulated, respectively. Conclusion Our results revealed that OIP5‐AS1 acts as a growth‐promoting lncRNA in lung cancer by suppressing miR‐378a‐3p function. OIP5‐AS1 and miR‐378a‐3p interaction may provide a potential target for lung cancer treatment.