Spermatogenesis and oogenesis basic helix-loop-helix (bHLH) transcription factor 2 (Sohlh2) functions as a bhlh transcription factor to regulate mouse germ cell differentiation. Our previous data showed that Sohlh2 was highly expressed in human normal tissues, but low level of Sohlh2 was observed in many cancer cell lines, suggesting a possible role of Sohlh2 in tumorigenesis. In this study, we examined this possibility by using immunohistochemistry, MTT, 5-bromo-2-deoxyuridine, clonogenic assay and tumor xenograft techniques. Our results showed that the expression of Sohlh2 was decreased in epithelial ovarian carcinoma (EOC) tissues compared with benign ovarian tumors and ovarian tumors with low malignant potential. Forced expression of Sohlh2 led to a significant reduction in cancer cell proliferation in vitro and tumorigenesis in nude mice. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell proliferation. Furthermore, Sohlh2 had opposite effects on its two direct targets p21 and cyclin D1: overexpression of Sohlh2 upregulated p21 but downregulated cyclin D1 expression. p21 knockdown could reverse the effects of Sohlh2 overexpression on inhibiting cell proliferation, and cyclin D1 knockdown could reverse the effects of Sohlh2 ablation on promoting cell proliferation. Thus, our data indicate that Sohlh2 likely functions as a tumor suppressor in EOCs, which is achieved by inducing p21 expression but repressing cyclin D1 expression.
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