Long Non-coding RNA FGD5-AS1 Regulates Cancer Cell Proliferation and Chemoresistance in Gastric Cancer Through miR-153-3p/CITED2 Axis
Yunhan Gao, Mubing Xie, Yi Guo, Qian Yang, Song Hu, Zhongfu Li
Abstract
Background: In this study, we investigated the molecular mechanisms of human long noncoding RNA (lncRNA) FYVE RhoGEF And PH Domain Containing 5 Antisense RNA 1 (FGD5-AS1) and its downstream epigenetic axis, human microRNA-153-3p (hsa-miR-153-3p) / Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) in human gastric cancer. Methods: Gastric cancer cell lines and clinical tumor samples were used to assess FGD5-AS1 expression levels. Lentivirus containing FGD5-AS1 small interfering RNA (sh-FGD5AS1) was applied to knockdown FGD5-AS1 expression. Cancer cell in vitro and in vivo proliferation, and 5-FU chemoresistance were assessed, respectively. Expressions of hsa-miR-153-3p / CITED2 was also assessed in FGD5-AS1-downregulated gastric cancer cells. Hsa-miR-153-3p was knocked down and CITED2 was upregulated to assess their directly functional correlations with FGD5-AS1 in gastric cancer. Results: Both gastric cancer cell lines and human tumor samples showed aberrant FGD5-AS1 upregulation. Lentiviral-induced FGD5-AS1 knockdown reduced cancer proliferation, 5-FU chemoresistance in vitro, and tumorigenicity in vivo. Hsa-miR-153-3p / CITED2 axis was confirmed to be downstream of FGD5-AS1 in gastric cancer. Hsa-miR-153-3p inhibition or CITED2 upregulation reversed the tumor-suppressing effects of FGD5-AS1 downregulation on gastric cancer proliferation and 5-FU chemoresistance. Conclusion: We demonstrated FGD5-AS1 can regulate human gastric cancer cell functions, possibly through its downstream epigenetic axis of hsa-miR-153-3p / CITED2.