TGF-β signaling promotes cervical cancer metastasis via CDR1as

Abstract

Abstract Background Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-β pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear. Methods After agonist of TGF-β treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed. Results CDR1as was found upregulated obviously following TGF-β activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-β signaling factors known to promote EMT, including P-Smad2 and P-Smad3. Conclusions Our study proved TGF-β signaling may promote cervical cancer metastasis via CDR1as.

Keywords

• Cervical cancer
• Metastasis
• TGF-β
• CDR1as
• Slug
• IGF2BP1