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Long Noncoding RNA TOB1-AS1 Represses Cervical Cancer Cell Proliferation, Invasion, and Migration via the
Yang Wang1, You-Xiang Hou2, Li Xie2
1Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Abstract:
Cervical cancer (CC) remains a major global health concern, particularly due to its aggressive nature and limited treatment options in advanced stages. Long noncoding RNA (lncRNA) TOB1-AS1 has been proposed as a tumor suppressor, yet its regulatory mechanism in CC remains unclear. This study aimed to elucidate the role of TOB1-AS1 in CC progression through the miR-27a-3p/thioredoxin-interacting protein (TXNIP) molecular axis. Functional gain- and loss-of-function assays were conducted to assess the effects of TOB1-AS1, miR-27a-3p, and TXNIP on cell proliferation, invasion, migration, and apoptosis. RT-qPCR, Western blotting, dual-luciferase reporter assays, and in vivo xenograft models were used to validate interactions and phenotypic outcomes. TOB1-AS1 was found to be downregulated in CC cells. Its overexpression suppressed proliferation, invasion, and migration, while enhancing apoptosis. Mechanistically, TOB1-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-27a-3p, thereby restoring TXNIP expression. Modulating miR-27a-3p or TXNIP levels partially reversed the effects of TOB1-AS1. In vivo, TOB1-AS1 overexpression significantly inhibited tumor growth and altered miR-27a-3p and TXNIP expression profiles. These findings suggest that lncRNA TOB1-AS1 acted as a ceRNA of miR-27a-3p to upregulate TXNIP, thereby suppressing CC cell proliferation, invasion and migration.
Insights
Long noncoding RNA TOB1-AS1 suppresses cervical cancer (CC) by acting as a ceRNA for miR-27a-3p, restoring TXNIP expression. This mechanism inhibits CC cell proliferation, invasion, and migration, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer (CC) poses a significant global health challenge, especially in advanced stages with limited therapeutic options.
- The tumor-suppressive role of long noncoding RNA (lncRNA) TOB1-AS1 in CC is suggested but its precise regulatory mechanism requires elucidation.
Purpose of the Study:
- To investigate the role of lncRNA TOB1-AS1 in cervical cancer (CC) progression.
- To elucidate the molecular mechanism involving the miR-27a-3p/thioredoxin-interacting protein (TXNIP) axis regulated by TOB1-AS1.
Main Methods:
- Functional gain- and loss-of-function assays were performed to evaluate the impact of TOB1-AS1, miR-27a-3p, and TXNIP on CC cell behaviors.
- RT-qPCR, Western blotting, and dual-luciferase reporter assays were utilized to confirm molecular interactions.
- In vivo xenograft models were employed to assess the therapeutic potential of TOB1-AS1 in CC tumor growth.
Main Results:
- TOB1-AS1 expression was found to be significantly downregulated in CC tissues and cells.
- Overexpression of TOB1-AS1 inhibited CC cell proliferation, migration, and invasion, while promoting apoptosis.
- TOB1-AS1 acted as a competing endogenous RNA (ceRNA) by sponging miR-27a-3p, leading to the restoration of TXNIP expression.
- In vivo studies confirmed that TOB1-AS1 overexpression suppressed tumor growth in xenograft models.
Conclusions:
- lncRNA TOB1-AS1 functions as a tumor suppressor in cervical cancer.
- The mechanism involves TOB1-AS1 acting as a ceRNA for miR-27a-3p to upregulate TXNIP, thereby inhibiting CC progression.
- Targeting the TOB1-AS1/miR-27a-3p/TXNIP axis presents a potential therapeutic strategy for cervical cancer.
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