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Published on: April 25, 2017
MiR-145-targeted HBXIP modulates human breast cancer cell proliferation
Yang Jiang1, Dan Wang2, Hui Ren3
1Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Background:
MiR-145 has been identified as a tumor suppressive microRNA in multiple cancers. In this current investigation, we searched for new direct targets of miR-145 and evaluated their effect on breast cancer development.
Methods:
Targetscan was used to predict the target genes of miR-145. The targeting of miR-145 on oncogenic HBXIP was verified by luciferase reporter gene analysis. The effect of miR-145 on the level of messenger RNA and protein of HBXIP was evaluated by quantitative real-time PCR and immunoblotting. Correlations between miR-145 and HBXIP, as well as miR-145 expression, were analyzed in 30 paired breast cancer and noncancerous tissues by quantitative real-time PCR. Methyl thiazol tetrazolium and colony formation assays were applied to determine the cell proliferation ability.
Results:
HBXIP was identified as a novel target gene of miR-145 in breast cancer. MiR-145 was found to dose-dependently decrease messenger RNA and protein expression of HBXIP in breast cancer MCF-7 cells. Notably, miR-145 expression was negatively related to HBXIP expression and was obviously reduced in breast cancer samples. Finally, miR-145 suppressed cell proliferation while its inhibitor, anti-miR-145, accelerated cell proliferation. Interestingly, silencing of HBXIP reversed the acceleration of cell proliferation induced by anti-miR-145 in breast cancer.
Conclusion:
Oncogenic HBXIP is a new direct target of tumor suppressive miR-145. Our findings reveal that miR-145-targeting HBXIP could be a potential therapeutic target in breast cancer.
Insights
MicroRNA-145 (miR-145) directly targets oncogenic HBXIP, suppressing breast cancer cell proliferation. This miR-145 targeting of HBXIP presents a potential therapeutic strategy for breast cancer treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNA-145 (miR-145) is recognized as a tumor suppressor in various cancers.
- Investigating novel direct targets of miR-145 is crucial for understanding breast cancer development.
Purpose of the Study:
- To identify new direct targets of miR-145 in breast cancer.
- To evaluate the functional impact of miR-145 and its targets on breast cancer progression.
Main Methods:
- Predicted miR-145 targets using Targetscan.
- Verified miR-145 targeting of HBXIP via luciferase reporter assays.
- Quantified gene and protein expression using qRT-PCR and immunoblotting.
- Analyzed miR-145 and HBXIP correlations in patient tissues.
- Assessed cell proliferation using MTT and colony formation assays.
Main Results:
- Identified HBXIP as a novel direct target of miR-145 in breast cancer.
- Demonstrated that miR-145 dose-dependently reduces HBXIP mRNA and protein levels.
- Observed an inverse correlation between miR-145 and HBXIP expression in breast cancer tissues.
- Showed that miR-145 inhibits cell proliferation, while its inhibition promotes it.
- Confirmed that HBXIP silencing reverses proliferation acceleration induced by anti-miR-145.
Conclusions:
- Oncogenic HBXIP is a newly identified direct target of the tumor-suppressive miR-145.
- Targeting HBXIP by miR-145 offers a promising therapeutic avenue for breast cancer.
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