title: REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells.
abstract: REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Polζ protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Polζ in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients.
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Obstetrics and Gynecology, Zhongshan Hospital Fudan University, Shanghai, China.
authors.forename: Tingyan
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Gynecology and Obstetrics, People's Hospital of Wuxi, Wuxi, Jiangsu, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Ren
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
mesh_terms: D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D004268:DNA-Binding Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human; D002945:Cisplatin