LncRNA FOXD2-AS1 as a Competitive Endogenous RNA against miR-150-5p Reverses Resistance to Sorafenib in Hepatocellular Carcinoma

Background/Aims: The current study elucidated the role of a long non-coding RNA (lncRNA), FOXD2-AS1, in the pathogenesis of hepatocellular carcinoma (HCC) and the regulatory mechanism underlying FOXD2-AS1/miR-150-5p/transmembrane protein 9 (TMEM9) signaling in HCC. Methods: Microarray analysis was used for preliminary screening of candidate lncRNAs in HCC tissues. qRT-PCR and Western blot analysis were used to detect the expression of FOXD2-AS1. Cell proliferation assays, luciferase assay, and RNA immunoprecipitation were performed to examine the mechanism by which FOXD2-AS1 mediates sorafenib resistance in HCC cells. Results: FOXD2-AS1 and TMEM9 were significantly decreased and miR-150-5p was increased in SR-HepG2 and SR-HUH7 cells compared with control parental cells. Overexpression of FOXD2-AS1 increased TMEM9 expression and overcame the resistance of SR-HepG2 and SR-HUH7 cells. Conversely, knockdown of FOXD2-AS1 decreased TMEM9 expression and increased the sensitivity of HepG2 and Huh7 cells to sorafenib. Our data also demonstrated that FOXD2-AS1 functioned as a sponge for miR-150-5p to modulate TMEM9 expression. Taken together, our findings revealed that FOXD2-AS1 is an important regulator of TMEM9 and contributed to sorafenib resistance. Thus, FOXD2-AS1 may serve as a therapeutic target against sorafenib resistance in HCC. Funding Statement: This study was supported by the Natural Science Foundation of Shanghai (17ZR1438000). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Shanghai Eastern Hepatobiliary Surgery Hospital Ethics Committee and written informed consent was obtained from all patients before tissue acquisition.