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HBx‐upregulated MAFG‐AS1 promotes cell proliferation and migration of hepatoma cells by enhancing MAFG expression and stabilizing nonmuscle myosin IIA
Author(s) -
Zhang Fang,
Li Yong,
Gan Lipeng,
Tong Xiaomei,
Qi Dandan,
Wang Qihui,
Ye Xin
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002374r
Subject(s) - downregulation and upregulation , hbx , microbiology and biotechnology , chemistry , cell growth , myosin , cell , cancer research , biology , transfection , biochemistry , gene
Abstract To identify hepatitis B virus (HBV)‐related lncRNA(s), we previously examined the transcription profiles of the HBV‐transgenic cell line HepG2‐4D14 and parental HepG2 cells by RNA deep sequencing and identified 38 upregulated long noncoding RNAs (lncRNAs). In the present study, the lncRNA MAFG‐AS1 is investigated in detail because its gene is located adjacent to the MAFG gene, which is an important transcription factor involved in cell proliferation. The level of MAFG‐AS1 is significantly higher in HCC tissue than in nontumor tissues. TCGA data show that the expression level of MAFG‐AS1 is negatively correlated with survival of HCC patients. GEO cohort data show that compared with healthy tissues, the expression level of MAFG‐AS1 is significantly higher in HBV‐infected liver tissues. Real‐time PCR and luciferase reporter assay data show that HBx can enhance the transcription of MAFG‐AS1. Gain‐of‐function and loss‐of‐function experiments indicate that MAFG‐AS1 promotes proliferation, migration, and invasion of HCC cells. Tumor formation assay results demonstrate that knockdown of MAFG‐AS1 significantly inhibits cell proliferation in nude mice. Furthermore, MAFG‐AS1 enhances the transcription of adjacent MAFG via E2F1. Additionally, MAFG‐AS1 interacts with three subunits (MYH9, MYL12B, and MYL6) of nonmuscle myosin IIA (NM IIA). Knockdown of MAFG‐AS1 inhibits ATPase activity of MYH9, interaction of NM IIA subunits, and cell cycle progression. Thus, the lncRNA MAFG‐AS1 is upregulated by HBV and promotes proliferation and migration of HCC cells. Our findings suggest that MAFG‐AS1 is a potential oncogene that may contribute to HBV‐related HCC development.