Metastasis is the primary reason of death in patients with cancer. Small nucleolar noncoding RNAs (snoRNAs) are conserved 60-300 nucleotide noncoding RNAs, involved in post-transcriptional regulation of mRNAs and noncoding RNAs. Despite their essential roles in cancer, the roles of snoRNAs in epithelial-mesenchymal transition (EMT)-induced metastasis have not been studied extensively. Here, we used small RNA sequencing to screen for snoRNAs related to EMT and breast cancer metastasis. We found a higher expression of SNORA71A in metastatic breast cancer tissues compared to nonmetastatic samples. Additionally, SNORA71A promoted the proliferation, migration, invasion and EMT of MCF-7 and MDA-MB-231 cells. Mechanistically, SNORA71A elevated mRNA and protein levels of ROCK2, a negative regulator of TGF-β signaling. Rescue assays showed ROCK2 abrogated the SNORA71A-mediated increase in proliferation, migration, invasion and EMT. Binding of SNORA71A to mRNA stability regulatory protein G3BP1, increased ROCK2 mRNA half-life. Furthermore, G3BP1 depletion abolished the SNORA71A-mediated upregulation of ROCK2. In vivo, SNORA71A overexpression promoted breast tumor growth, and SNORA71A knockdown inhibited breast cancer growth and metastasis. We suggest SNORA71A enhances metastasis of breast cancer by binding to G3BP1 and stabilizing ROCK2.
Keywords: ROCK2; SNORA71A; breast cancer; epithelial-mesenchymal transition; snoRNA.
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.