miR-378c suppresses Wilms tumor development via negatively regulating CAMKK2

Abstract

Wilms tumor is a rare kidney malignancy primarily developed in children. Treatment for Wilms tumor includes surgery, radiotherapy, and chemotherapy. Recent studies have demonstrated that microRNAs (miRNAs) play important roles in regulating Wilms tumor development. In this study, we aimed to elucidate the expression and function of miR-378c in Wilms tumor. Quantitative real-time PCR (qRT-PCR) results showed that miR-378c was downregulated in Wilms tumor tissues and cell lines. Functionally, further CCK-8, would healing, and transwell assays revealed that overexpression of miR-378c impaired Wilms tumor cell growth and metastasis in vitro. In addition, xenograft assay showed that miR-378c overexpression inhibited Wilms tumor development in vivo. Mechanistically, luciferase reporter assay confirmed that miR-378c directly targets CAMKK2 in Wilms tumor. qRT-PCR and western blot assays demonstrated that CAMKK2 was highly expressed in Wilms tumor tissues and cell lines. Rescue experiments were performed to further evaluate the functional relationship between miR-378c and CAMKK2. Overexpression of miR-378c suppressed Wilms tumor cell metastasis via negatively regulating CAMKK2 expression. Consistently, inhibition of miR-378c enhanced Wilms tumor cell malignancy behavior via augmenting CAMKK2 expression, which could be abrogated by CAMKK2 knockdown. In summary, our findings suggest that miR-378c inhibits the development and metastasis of Wilms tumor via negatively regulating CAMKK2 expression, which could be utilized to develop new therapy strategy.

Keywords: CAMKK2; Wilms tumor; miR-378c.