Silencing of KCNK15-AS1 inhibits lung cancer cell proliferation via upregulation of miR-202 and miR-370.

Abstract

Lung cancer is the most common cause of cancer-associated mortality globally. Long non-coding RNAs (lncRNAs) are transcripts with a length of >200 nucleotides, which are not translated into proteins. Growing evidence has indicated that certain lncRNAs are associated with various biological processes in cancer. However, the functions of KCNK15 and WISP2 antisense RNA 1 (KCNK15-AS1) in lung cancer carcinogenesis and progression have remained elusive. The present study indicated that KCNK15-AS1 was overexpressed in lung adenocarcinoma tissues compared with paracancerous normal tissues, and the high expression of KCNK15-AS1 was significantly associated with poor prognosis compared with the patients with low expression (P<0.001). Furthermore, the knockdown of KCNK15-AS1 was performed in A549 and H460 lung cancer cells with small interfering RNA, resulting in a significant inhibition of the proliferation, a decrease in the mRNA and protein expression of cyclin D1 (CCND1) and epidermal growth factor receptor (EGFR), in addition to the phosphorylation of protein kinase B, with a concomitant increase in the expression of microRNA (miR)-202 and miR-370 compared with negative control group. Rescue experiments demonstrated that the inhibition of miR-202 or miR-370 partially recovered the EGFR and CCND1 expression and the proliferation rates, which were reduced by KCNK15-AS1 silencing. In conclusion, these results suggested that KCNK15-AS1 functions as an oncogene via regulating the miR-202/miR-370/EGFR axis in lung cancer and may provide a potential target for lung cancer treatment.