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Published on: March 30, 2019
Lnc-STYK1-2 regulates bladder cancer cell proliferation, migration, and invasion by targeting miR-146b-5p expression
Ranran Dai1, Qingping Jiang2, You Zhou1
1Guangdong Key Laboratory of Urology, Guangzhou Medical University, Guangzhou, China.
Background:
Epigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood. This study investigated the role of long noncoding RNA (lncRNA) lnc-STYK1-2 in tumorigenesis in cancerous bladder cells.
Methods:
Differential lncRNA and mRNA profiles were characterized by high-throughput RNA sequencing combined with validation via quantitative PCR. Bladder cancer cell proliferation was assessed through MTS, and bladder cancer cell migration and invasion were assessed through a Transwell system. The in vivo tumorigenesis of bladder cancer cells was evaluated using the cancer cell line-based xenograft model. The dual-luciferase reporter assay verified the association of miR-146b-5p with lnc-STYK1-2 and the target gene. Protein abundances and phosphorylation were detected by Western blotting.
Results:
Alterations in lncRNA profiles, including decreased lnc-STYK1-2 expression, were detected in bladder cancer tissues compared with adjacent noncancerous tissues. lnc-STYK1-2 silencing effectively promoted proliferation, migration, and invasion in two bladder cancer cell lines, 5637 and T24, and their tumorigenesis in nude mice. lnc-STYK1-2 siRNA promoted miR-146b-5p and reduced ITGA2 expression in bladder cancer cells. Moreover, miR-146b-5p suppressed ITGA2 expression in bladder cancer cells through direct association. Also, lnc-STYK1-2 directly associated with miR-146b-5p. Finally, miR-146b-5p inhibitors abrogated the alterations in bladder cell functions, ITGA2 expression, and phosphorylation of AKT, STAT3, and P65 proteins in 5637 and T24 cells induced by lnc-STYK1-2 silencing.
Conclusion:
lnc-STYK1-2 inhibited bladder cancer cell proliferation, migration, and tumorigenesis by targeting miR-146b-5p to regulate ITGA2 expression and AKT/STAT3/NF-kB signaling.
Insights
Long noncoding RNA (lncRNA) lnc-STYK1-2 suppresses bladder cancer progression. It inhibits cell proliferation, migration, and tumorigenesis by regulating miR-146b-5p and ITGA2 expression.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Noncoding RNAs play a role in cancer development.
- The involvement of noncoding RNAs in bladder cancer is not well understood.
- This study focuses on the long noncoding RNA (lncRNA) lnc-STYK1-2 in bladder cancer.
Purpose of the Study:
- Investigate the role of lnc-STYK1-2 in bladder cancer tumorigenesis.
- Determine the molecular mechanisms underlying lnc-STYK1-2's function.
- Identify potential therapeutic targets for bladder cancer.
Main Methods:
- RNA sequencing and quantitative PCR for lncRNA and mRNA profiling.
- Cell proliferation, migration, and invasion assays (MTS, Transwell).
- In vivo xenograft models, dual-luciferase reporter assays, and Western blotting.
Main Results:
- lnc-STYK1-2 expression is decreased in bladder cancer tissues.
- Silencing lnc-STYK1-2 promotes bladder cancer cell proliferation, migration, invasion, and tumorigenesis.
- lnc-STYK1-2 targets miR-146b-5p, which in turn regulates ITGA2 expression and downstream signaling pathways (AKT/STAT3/NF-kB).
Conclusions:
- lnc-STYK1-2 acts as a tumor suppressor in bladder cancer.
- The lnc-STYK1-2/miR-146b-5p/ITGA2 axis is crucial for regulating bladder cancer cell behavior.
- Targeting this pathway may offer a novel therapeutic strategy for bladder cancer.
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