Abstract
SOX4, a member of the SOX (sex-determining region Y-related HMG box) transcription factor family, has been reported to be abnormally expressed in a wide variety of cancers, and to exert a pleiotropic function. However, its function in progression of cervical cancer (CC) remains unknown. In this study, we found that SOX4 was highly expressed in CC cells and tissues, and overexpression of SOX4 in CC CaSki cells enhanced tumor clone formation and cell proliferation, and accelerated cell cycle progress. Meanwhile, downregulation of SOX4 by shRNA in CaSki cells inhibited cell proliferation, and slowed cell cycle progress, indicating that SOX4 contributes to the development of CC. In addition, SOX4 overexpression by gene transfer reduced the sensitivity of CaSki cells in response to the chemotherapeutic drug cisplatin, and SOX4 downregulation by RNA interference increased the sensitivity of CaSki cells in response to cisplatin. Moreover, SOX4 overexpression upregulated multiple drug resistant gene ABCG2, and SOX4 downregulation inhibited ABCG2 expression. Taken together, these results suggested that SOX4 functions to modulate cancer proliferation by regulation of cell cycle, and inhibit cancer cell sensitivity to therapeutic drug via upregulation of ABCG2. Thus, SOX4 may be a target for CC chemotherapy.
Highlights
The SOX (sex-determining region Y (SRY)-related highmobility-group (HMB) box transcription factor) gene family is found throughout the animal kingdom
SOX4 expression has been discovered in various carcinomas, its role in CC is not well defined
The expression of SOX4 was analyzed by immunohistochemistry in 31 cervical squamous carcinoma samples and their paired adjacent normal tissues (Figure 1b)
Summary
The SOX (sex-determining region Y (SRY)-related highmobility-group (HMB) box transcription factor) gene family is found throughout the animal kingdom. Multiple studies have revealed aberrant expression of SOX4 in several human cancers. Mesenchymal transition and results in a cancer stem cell-like phenotype in breast cancer cells.[11] a reduced expression of SOX4 was detected in cancer of cutaneous melanoma,[12] primary gallbladder carcinoma[13] and colon cancer,[14] and SOX4 has a cancer suppressor gene role. The ability of cells to acquire resistance to multiple drugs is often mediated by overexpression of ATP-binding cassette (ABC) transporters that remove drugs out of the cells and reduce intracellular drug levels.[15] The human ABCG2 gene is located on chromosome. ABCG2 is used as a marker for cancer stem cells or cancer-initiating cells in various human cancers.[25,26]
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