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LncRNA TTN-AS1 acts as sponge for miR-15b-5p to regulate FBXW7 expression in ovarian cancer
Sheng Miao1, Jia Wang1, Lili Xuan1
1Department of Gynaecology and Obstetrics, China-Japan Union Hospital of Jilin University, Changchun, China.
Abstract:
Emerging evidence showed that long noncoding RNA (lncRNA) plays crucial roles in regulating various cancer biological behaviors. Titin-antisense RNA1 (TTN-AS1) has been reported to have crucial roles in cancers but its role in ovarian cancer remains unknown. The levels of TTN-AS1, microNRA-15b-5p (miR-15b-5p), and F-box and WD repeat domain containing 7 (FBXW7) in ovarian cancer cells were measured by quantitative reverse-transcription PCR. Targets for TTN-AS1 and miR-15b-5p were predicted by bioinformatic tools, and validated by luciferase activity reporter assay. Cell proliferation, colony formation, and cell apoptosis were analyzed with cell counting kit-8 assay, colony formation assay, and flow cytometry. Correlation of TTN-AS1 and FBXW7 was analyzed at gene expression profiling interactive analysis. TTN-AS1 was found decreased expression in ovarian cancer tissues and cells. Dual-luciferase activity validated TTN-AS1 and FBXW7 shared binding site in miR-15b-5p. Functional assays showed TTN-AS1 overexpression inhibits ovarian cancer cell proliferation, colony formation but promotes apoptosis. Rescue experiments showed that knockdown of FBXW7 could partially counteracted the effects of TTN-AS1 overexpression on ovarian cancer cell behaviors. Our results indicated that the TTN-AS1/miR-15b-5p/FBXW7 axis identified in this work could help to identify treatment biomarkers for ovarian cancer.
Insights
Titin-antisense RNA1 (TTN-AS1) acts as a tumor suppressor in ovarian cancer by inhibiting cell proliferation and promoting apoptosis. This long noncoding RNA regulates the miR-15b-5p/FBXW7 axis, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in cancer progression.
- The role of Titin-antisense RNA1 (TTN-AS1) in ovarian cancer was previously unknown.
Purpose of the Study:
- To investigate the function and mechanism of TTN-AS1 in ovarian cancer.
- To explore the potential regulatory axis involving TTN-AS1, miR-15b-5p, and FBXW7.
Main Methods:
- Quantitative reverse-transcription PCR to measure gene expression.
- Bioinformatic prediction and luciferase reporter assays to validate interactions.
- Cell proliferation, colony formation, and apoptosis assays to assess functional effects.
Main Results:
- TTN-AS1 expression was decreased in ovarian cancer tissues and cells.
- TTN-AS1, miR-15b-5p, and FBXW7 were validated as interacting components.
- Overexpression of TTN-AS1 suppressed ovarian cancer cell proliferation and colony formation while promoting apoptosis.
Conclusions:
- The TTN-AS1/miR-15b-5p/FBXW7 axis plays a significant role in ovarian cancer.
- TTN-AS1 functions as a tumor suppressor in ovarian cancer.
- This axis may serve as a potential therapeutic biomarker for ovarian cancer treatment.
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