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

doi:10.3389/fgene.2020.00715

Long Non-coding RNA FGD5-AS1 Regulates Cancer Cell Proliferation and Chemoresistance in Gastric Cancer Through miR-153-3p/CITED2 Axis

Front Genet. 2020 Aug 11:11:715. doi: 10.3389/fgene.2020.00715. eCollection 2020.

Authors

Yunhan Gao¹, Mubing Xie², Yi Guo¹, Qian Yang¹, Song Hu¹, Zhongfu Li¹

Affiliations

¹ Department of General Surgery, Chongqing University Central Hospital, Chongqing Emergency Medical Center, The Fourth People's Hospital of Chongqing, Chongqing, China.
² Department of General Surgery, Yongchuan Dakang Hospital of Traditional Chinese Medicine, Chongqing, China.

Abstract

Background: In this study, we investigated the molecular mechanisms of human long non-coding 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 cells in vitro and in vivo proliferation, and 5-FU chemoresistance were assessed, respectively. Expressions of hsa-miR-153-3p/CITED2 were also assessed in FGD5-AS1-downregulated gastric cancer cells. Hsa-miR-153-3p was knocked down and CITED2 was upregulated to assess their direct 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 that FGD5-AS1 can regulate human gastric cancer cell functions, possibly through its downstream epigenetic axis of hsa-miR-153-3p/CITED2.

Keywords: CITED2; FGD5-AS1; gastric cancer; lncRNA; miR-153-3p; miRNA.