Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer

Liu,Dan; Zhang,Xiao-Xue; Xi,Bi-Xin; Wan,Dong-Yi; Li,Li; Zhou,Jin; Wang,Wei; Ma,Ding; Wang,Hui; Gao,Qing-Lei

doi:10.3892/ijo.2014.2510

Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer

Authors:
- Dan Liu
- Xiao-Xue Zhang
- Bi-Xin Xi
- Dong-Yi Wan
- Li Li
- Jin Zhou
- Wei Wang
- Ding Ma
- Hui Wang
- Qing-Lei Gao
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Affiliations: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University Guangzhou, Guangzhou, P.R. China
Published online on: June 20, 2014 https://doi.org/10.3892/ijo.2014.2510
Pages: 1232-1240

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Abstract

Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression. Here we report that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in DNA replication of cervical cancer cells. The expression of SIX1 was induced by the E7 oncoprotein of human papillomaviruses in cervical intraepithelial neoplasia and cervical cancer. The increase of SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication, including the genes coding for the proteins in minichromosome maintenance complex (MCM2, MCM3, MCM6), DNA polymerase α-primase complex (POLA1, PRIM1, PRIM2), clamp loader (RFC3, RFC4, RFC5), DNA polymerase δ complex (POLD3) and DNA polymerase ε complex (POLE2). In line with this, the increase of SIX1 expression enhanced DNA synthesis, accelerated G1 to S phase progression, and promoted the proliferation of cervical cancer cells and the growth of cervical cancer. Consistently, knockdown of SIX1 could hamper DNA synthesis, slow down G1 to S phase progression, and suppress tumor cell proliferation and tumor growth. Importantly, SIX1 could more efficiently promote anchorage-independent cell growth. These results suggest that the increase of SIX1 expression could promote tumorigenesis, progression and invasive growth of cervical cancer by promoting DNA replication, and that targeting SIX1 may have significant therapeutic value in cervical cancer treatment.

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