RHOXF1/TSGA10 axis: a possible molecular mechanism of carcinogenesis.

TSGA10 has recently been highlighted as an important factor in spermatogenesis with critical roles during sperm maturation. Although up-regulation of TSGA10 expression in early stages and its down-regulation in advanced stages of some cancers has already been demonstrated, the regulatory mechanism governing its expression has not yet been elucidated. RHOXF1 transcription factor is known to be a cancer/testis antigen with vital roles in spermatogenesis. Besides, both RHOXF1 and TSGA10 are cancer/testis antigens that are involved in the carcinogenic processes. Given that RHOXF1 is a transcription factor; and both RHOXF1 and TSGA10 are highly expressed in round spermatids during the transition of meiotic to post-meiotic stages of spermatogenesis, we aimed to investigate RHOXF1 knockdown effect on the expression levels of TSGA10. RHOXF1 shRNA vector was prepared and transient transfected into MCF7 cells that exhibit high expression of RHOXF1 and TSGA10. The efficiency of transfection was assessed by real-time PCR for evaluation of RHOXF1 knock down. TSGA10 expression was also measured. Untransfected cells and cells transfected with empty vector as well as scrambled vector were used as control. Our data showed that shRNA-mediated knockdown of RHOXF1 expression led to decreased expression levels of TSGA10. We found the positive co-expression of RHOXF1 and TSGA10 in all normal tissues as well as in variety of cancer tissues, with the highest positive co-expression in pancreas, breast, and kidney cancers. Therefore, TSGA10 expression might be regulated by RHOXF1 transcription factor. Future studies are needed to elaborate whether this regulatory role is exerted directly or indirectly. The results of this study might broaden understanding of transcriptional regulation in cancer biology and facilitate novel strategies to overcome the effects of oncogenic transcription factors on their targets.