Ring-finger protein RNF126 promotes prostate cancer progression via regulation of MBNL1

Purpose: Aberrant activation/overexpression of RNF126 is implicated as a driving event in tumor progression. However, although some functions of RNF126 in prostate Cancer (PCa) cell lines has been reported, more biological functions and in-depth mechanisms should be further clarified in PCa.

Methods: Here, we provide evidence that RNF126 expression is elevated in human PCa tissues and cell lines, which is associated with tumor grades and prognosis. Cell proliferation was measured by the CCK8 and colony-formation assays. Cell migration was performed by Transwell and wound-healing assays. RNF126 target proteins were investigated via proteomic, co-immunoprecipitation and western blot methods. Additionally, we knock-downed MBNL1 expression to perform rescue experiments. In vivo, xenograft mice assay was used to verify the effect of RNF126 on the growth of PCa cell.

Results: Here, we showed that RNF126 was highly expressed in PCa and its higher expression was associated with worse patients' prognosis. Expression modulation of RNF126 affects PCa cells proliferation, migration, EMT and docetaxel (DTX) resistance in vitro or in vivo. Additionally, RNF126 involves in the regulation of PI3K/Akt, MEK/ERK and EMT pathways. Mechanistically, immunoprecipitation (IP) and coimmunoprecipitation (co-IP) assays indicated that RNF126 could bind to MBNL1 directly. Our data also suggested that MBNL1 was a critical downstream event in RNF126-mediated tumorigenesis and chemo-resistance and played a crucial role in driving the PI3K/Akt, MEK/ERK and EMT pathways.

Conclusion: Taken together, our findings reveal a novel biological and molecular functions of RNF126 and may provide a new treatment option for PCa patients.

Chemo-resistance; MBNL1; Prognosis; Prostate cancer; RNF126; Signaling pathways.