Silencing of the long non-coding RNA RHPN1-AS1 suppresses the epithelial-to-mesenchymal transition and inhibits breast cancer progression

摘要

Breast cancer (BC) is a frequently diagnosed malignancy in women. Increasing evidence implicates mis-expression of the long non-coding RNA (lncRNA) RHPN1 antisense RNA 1 (RHPN1-AS1) in the development of multiple cancer types. However, little is known about the expression pattern and function of lncRNA RHPN1-AS1 in the pathobiology of BC. We evaluated the expression of RHPN1-AS1 in The Cancer Genome Atlas dataset, and analyzed associations between RHPN1-AS1 expression and clinicopathologic features of BC patients. Additionally, we compared the expression of RHPN1-AS1 between BC and breast non-tumor samples via quantitative real-time polymerase chain reaction, and in situ hybridization, and evaluated the prognostic value of RHPN1-AS1 in a BC tissue microarray. We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells in vitro, and tumor growth in vivo. Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion in vitro, and reduced tumor growth in xenograft models. Furthermore, RHPN1-AS1 silencing was associated with a decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers in the xenograft tumors, suggesting that RHPN1-AS1 promotes invasion in BC cells by enhancing EMT. These findings suggest that RHPN1-AS1 is a potential prognostic biomarker and therapeutic target for BC.