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Updated: Jan 5, 2026

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
The Multifunction Of miR-218-5p-Cx43 Axis In Breast Cancer
Chen Xia1, Hong Jiang2, Fugui Ye3
1Department of Medical Oncology, Hepatobiliary and Pancreatic Unit, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People's Republic of China.
Background:
Gemcitabine is proven to be the first-line standard treatment of breast cancers. Yet, little is known involving gemcitabine resistance and remains largely to be elucidated.
Materials And Methods:
We evaluated the expression of Cx43 in gemcitabine-resistant cells and parental cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Dual-luciferase reporter assay was applied to examine the epigenetic regulator of Cx43. The role of miR-218-5p-Cx43 axis on cell cytotoxicity, cell proliferation, colony formation, chemoresistance and migration was detected via mammalian expression vector and small short RNA (shRNA) transfection in vitro.
Results:
In this study, we found that Cx43 expression levels were significantly lower in gemcitabine-resistant cells than in the parental cells. On deep investigation of the epigenetic regulation of Cx43, a few miRNA candidates targeting Cx43 were derived. Through dual-luciferase reporter assay, Cx43 was proved to be a direct target of miR-218-5p. Besides, qPCR, Western blot demonstrated an inverse correlation between miR-218-5p and Cx43 expression in breast cancer cells, thus forming the miR-218-5p-Cx43 axis. Notably, miR-218-5p-Cx43 axis was found to be involved in the process of gemcitabine chemoresistance, cell proliferation and migration in breast cancer cells.
Conclusion:
Our findings suggested that miR-218-5p-Cx43 axis was versatile and indicated significant potency in breast cancer cells. More importantly, miR-218-5p-Cx43 axis might be valuable in translational medicine, with therapeutic and prognostic information.
Insights
The miR-218-5p-Cx43 axis plays a key role in gemcitabine resistance in breast cancer. Understanding this axis offers potential for new therapeutic strategies against chemoresistant breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gemcitabine is a standard first-line treatment for breast cancer.
- Mechanisms underlying gemcitabine resistance in breast cancer remain largely unknown.
Purpose of the Study:
- To investigate the role of Connexin 43 (Cx43) in gemcitabine resistance.
- To elucidate the epigenetic regulation of Cx43 and its involvement in breast cancer progression and chemoresistance.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were used to assess Cx43 expression.
- Dual-luciferase reporter assays identified miR-218-5p as a direct regulator of Cx43.
- In vitro experiments using mammalian expression vectors and small short RNA (shRNA) evaluated the functional impact of the miR-218-5p-Cx43 axis.
Main Results:
- Cx43 expression was significantly lower in gemcitabine-resistant breast cancer cells compared to parental cells.
- An inverse correlation was observed between miR-218-5p and Cx43 expression, establishing the miR-218-5p-Cx43 axis.
- This axis was implicated in gemcitabine chemoresistance, cell proliferation, and migration.
Conclusions:
- The miR-218-5p-Cx43 axis is a significant factor in breast cancer.
- This axis holds potential for therapeutic and prognostic applications in translational medicine for breast cancer treatment.
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