Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.691140
Keywords
SPINT1-AS1; cervical cancer; progression; miR-214 biogenesis; Wnt/beta-catenin signaling
Categories
Funding
- Maternal and Child Health Care Research Projects of Jiangsu Province [F201349, F201948, F202003]
- Key Research Program (Agriculture and social development) of Xuzhou Science and Technology Bureau [KC19138]
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Accumulating evidence has shown dysregulated expression and critical roles of non-coding RNAs in various malignancies, including cervical cancer. In this study, a novel cervical cancer-associated lncRNA called SPINT1-AS1 was identified, which represses miR-214 biogenesis and activates Wnt/β-catenin signaling to promote cervical cancer progression.
Accumulating evidences have revealed the dysregulated expressions and critical roles of non-coding RNAs in various malignancies, including cervical cancer. Nevertheless, our knowledge about the vast majority of non-coding RNAs is still lacking. Here we identified long non-coding RNA (lncRNA) SPINT1-AS1 as a novel cervical cancer-associated lncRNA. SPINT1-AS1 was increased in cervical cancer and correlated with advanced stage and poor prognosis. SPINT1-AS1 was a direct downstream target of miR-214, a well-known tumor suppressive microRNA (miRNA) in cervical cancer. Intriguingly, SPINT1-AS1 was also found to repress miR-214 biogenesis via binding DNM3OS, the primary transcript of miR-214. The interaction between SPINT1-AS1 and DNM3OS repressed the binding of DROSHA and DGCR8 to DNM3OS, blocked DNM3OS cleavage, and therefore repressed mature miR-214 biogenesis. The expression of SPINT1-AS1 was significantly negatively correlated with miR-214 in cervical cancer tissues, supporting the reciprocal repression between SPINT1-AS1 and miR-214 in vivo. Through downregulating mature miR-214 level, SPINT1-AS1 upregulated the expression of beta-catenin, a target of miR-214. Thus, SPINT1-AS1 further activated Wnt/beta-catenin signaling in cervical cancer. Functionally, SPINT1-AS1 drove cervical cancer cellular proliferation, migration, and invasion in vitro, and also tumorigenesis in vivo. Deletion of the region mediating the interaction between SPINT1-AS1 and DNM3OS, overexpression of miR-214, and inhibition of Wnt/beta-catenin signaling all reversed the roles of SPINT1-AS1 in cervical cancer. Collectively, these findings identified SPINT1-AS1 as a novel cervical cancer-associated oncogenic lncRNA which represses miR-214 biogenesis and activates Wnt/beta-catenin signaling, highlighting its potential as prognostic biomarker and therapeutic target for cervical cancer.
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