MicroRNA-1298-3p induces tumor-suppressive effects in human cervical cancer cells via post-transcriptional suppression of ONECUT2

Abstract

Recent studies have revealed the negative regulatory role of microRNA-1298-3p (miR-1298-3p) in human carcinogenesis. However, the role of miR-1298-3p is yet to be studied in cervical cancer. The present study showed significant (P=0.03) downregulation of miR-1298-3p in human cervical cancer cell lines. Overexpression of miR-1298-3p significantly (P=0.02) suppressed the proliferation of the cervical cancer cells via induction of apoptosis. The percentage of early and late apoptotic cervical cancer cells increased from 3.33% to 43.37% upon miR-1298-3p overexpression. Additionally, expression of Bax was increased and that of Bcl-2 was decreased in miR-1298-3p overexpressing cervical cancer cells. Overexpression of miR-1298-3p could also suppress migration and invasion of the cervical cancer cells. In vivo study showed that miR-1298-3p overexpression significantly (P=0.02) inhibited the xenografted tumor-growth via induction of apoptosis. In silico analysis and subsequent in vitro assays revealed that miR-1298-3p exerts its effects by targeting the expression of ONECUT2. While silencing of ONECUT2 could suppress the proliferation of cervical cancer cells, its overexpression could nullify the tumor-suppressive effects of miR-1298-3p. Collectively, the results revealed the tumor-suppressive role of miR-1298-3p in cervical cancer .and thus, indicative of its future therapeutic utility.