title: HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α.
abstract: Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). Emerging evidence has shown the association between aberrantly expressed miR-221 and cancer development; however, little is known concerning its potential role in hepatitis B virus (HBV)-related HCC. In the present study, functional studies demonstrated that HBx leads to the promotion of cell proliferation and cell growth viability. Obviously overexpressed miR-221 was found in HBx-transfected cells compared with the mock counterparts. Suppression of miR-221 significantly inhibited HCC cell proliferation. Western blot analysis indicated that estrogen receptor-α (ERα) was downregulated in HCC tissues and cell lines. Bioinformatic analysis combined with validation experiments identified ERα as a direct target of miR-221. The present study suggests that miR-221 modulates HCC cancer cell proliferation by suppressing ERα, functioning as a tumor promoter. Moreover, our data imply that miR-221 has potential as an miRNA-based therapeutic target for HBV-related HCC.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Yi-Shu
authors.initials: YS
authors.lastname: Tang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Jian-Gang
authors.initials: JG
authors.lastname: Ai
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C506487:ESR1 protein, human; C525709:MIR221, human; C057628:hepatitis B virus X protein