SNHG5 enhances Paclitaxel sensitivity of ovarian cancer cells through sponging miR-23a

Background: Ovarian cancer is one of the most lethal gynecological malignancies throughout the world. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been reported to play an important role in several human cancers, but the role of SNHG5 in the chemoresistance of ovarian cancer cells is yet elusive.

Method: The expression of SNHG5 and miR-23a were determined by quantitative reverse transcriptase polymerase chain reaction. The effects of SNHG5 and miR-23a on the sensitivity of ovarian cancer cells to paclitaxel (PTX) were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. The subcellular location of SNHG5 was detected by a subcellular fraction assay. The interaction between SNHG5 and miR-23a was determined by luciferase reporter assay and RNA immunoprecipitation assay.

Results: The expression of SNHG5 was downregulated in the cancer genome atlas cohort. Similarly, decreased expression of SNHG5 was observed in ovarian cancer tissues. Moreover, lower expression of SNHG5 was found in PTX-resistant ovarian cancer patients as well as PTX-resistant ovarian cancer cell lines. Downregulation of SNHG5 expression was indicative of poor prognosis in patients with ovarian cancer. Overexpression of SNHG5 enhanced the sensitivity of SKOV3/PTX and HeyA-8/PTX cells to PTX in vitro and enhanced PTX sensitivity in tumors in vivo. Interestingly, an inverse correlation between SNHG5 and miR-23a expression was found in ovarian cancer tissues and SNHG5 functioned as a decoy for miR-23a. Silencing of miR-23a overcame the resistance of SKOV3/PTX and HeyA-8/PTX cells to PTX. More importantly, miR-23a overexpression could reverse the inductive effect of SNHG5 overexpression on PTX sensitivity of ovarian cancer cells.

Conclusion: SNHG5 enhanced the sensitivity of ovarian cancer cells to PTX through sponging miR-23a, providing a new mechanism of chemoresistance in ovarian cancer.