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Published on: August 23, 2019
SPINT1-AS1 Drives Cervical Cancer Progression via Repressing miR-214 Biogenesis
Hongjuan Song1,2, Yuan Liu1, Hui Liang3
1Department of Gynecology, Xuzhou Maternal and Child Health Care Hospital, Xuzhou, China.
Abstract:
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 β-catenin, a target of miR-214. Thus, SPINT1-AS1 further activated Wnt/β-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/β-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/β-catenin signaling, highlighting its potential as prognostic biomarker and therapeutic target for cervical cancer.
Insights
Long non-coding RNA SPINT1-AS1 promotes cervical cancer by repressing miR-214 biogenesis and activating Wnt/β-catenin signaling. SPINT1-AS1 may serve as a prognostic biomarker and therapeutic target for cervical cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-coding RNAs (ncRNAs) play crucial roles in various cancers, but many remain uncharacterized.
- Cervical cancer exhibits dysregulated ncRNA expression, necessitating further investigation into novel regulatory mechanisms.
- Long non-coding RNA (lncRNA) SPINT1-AS1 is identified as a novel player in cervical cancer pathogenesis.
Purpose of the Study:
- To identify and characterize novel lncRNAs involved in cervical cancer.
- To elucidate the molecular mechanism by which SPINT1-AS1 influences cervical cancer progression.
- To evaluate the potential of SPINT1-AS1 as a prognostic biomarker and therapeutic target.
Main Methods:
- Identification of SPINT1-AS1 in cervical cancer tissues.
- Investigation of the regulatory relationship between SPINT1-AS1, miR-214, and Wnt/β-catenin signaling pathway.
- Functional assays including proliferation, migration, invasion, and tumorigenesis studies in vitro and in vivo.
Main Results:
- SPINT1-AS1 expression is upregulated in cervical cancer and correlates with advanced stage and poor prognosis.
- SPINT1-AS1 represses miR-214 biogenesis by interfering with the processing of its primary transcript (DNM3OS).
- SPINT1-AS1 upregulates β-catenin by downregulating miR-214, thereby activating Wnt/β-catenin signaling and promoting cancer progression.
Conclusions:
- SPINT1-AS1 acts as an oncogenic lncRNA in cervical cancer by inhibiting miR-214 and activating Wnt/β-catenin signaling.
- SPINT1-AS1 demonstrates potential as a prognostic biomarker for cervical cancer patients.
- Targeting SPINT1-AS1 offers a potential therapeutic strategy for cervical cancer treatment.
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