title: Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.
abstract: Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in ovarian cancer cell lines. Impact statement We found that hepatitis B X-interacting protein (HBXIP) was able to activate the CD147 promoter through Sp1. In vivo, depletion of HBXIP decreased the tumor volume and weight induced by CP. Taken together, these results indicate that HBXIP promotes cisplatin resistance and regulated CD147 via Sp1 in ovarian cancer cell lines.
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Biliang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051926:Basigin / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C497886:BSG protein, human; D007136:Immunoglobulins; D009687:Nuclear Proteins; C452851:RSF1 protein, human; C090698:SP1 antigen; D015534:Trans-Activators; D051926:Basigin; D053148:Caspase 3; D002945:Cisplatin
keywords: CD147; Hepatitis B X-interacting protein; Sp1; chemoresistance; cisplatin; ovarian cancer