BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer.
Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC). B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3), a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is mediated by its downstream target gene, STAT3.
Department of Gynecology and Obstetrics.
Hu
H
Zhao
Department of Gynecology and Obstetrics.
Wuliang
W
Wang
Department of Gynecology and Obstetrics.
Qinghe
Q
Zhao
Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Guiming
G
Hu
Department of Gynecology and Obstetrics.
Kehong
K
Deng
Department of Gynecology and Obstetrics.
Yuling
Y
Liu
B-cell CLL/lymphoma 3; cell cycle; cell proliferation; cervical carcinoma; signal transducer and activator of transcription 3