Dysregulation of miR145-SOX9-CDK4 Axis in Prostate Adenocarcinoma

The transcription factor SRY-related high mobility group box 9 (SOX9) plays a pivotal role in tumorigenesis and cancer progression. SOX9 is expressed in fetal prostate tissues, downregulated in mature prostate tissues, and reactivated in prostate cancer by a mechanism that is not completely elucidated. Our previous study showed that miR145 is downregulated in prostate cancer. Here we prove that miR145 downregulates SOX9 by targeting its 3′-untranslated region. The knockdown of SOX9 using RNAi induces cell cycle arrest at the G0/G1 phase and inhibits prostate cancer cell proliferation. Furthermore, on probing the regulatory mechanisms of SOX9, we found that cyclin-dependant kinase (CDK) 4 is a novel target gene regulated by the transcription factor SOX9, which interacts with SOX9 binding sites in the CDK4 promoter region. Collectively, these results show that the overexpression of SOX9 and CDK4 are essential factors in prostate tumorigenesis and cancer progression. Therefore, the regulation of the microRNA (miR) 145–SOX9–CDK4 pathway may constitute the potential therapy for prostate cancer.Funding Information: Key research and development projects of Sichuan Science and Technology Department (serial number 2022YFS0135).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: Approvals from Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China were obtained before initiating this study. Written informed consents for the use of clinical data, images, and permission for publication were obtained from the patients. Written informed consent was obtained from the patient for publication of cases and any accompanying images.