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Circ_0069094 regulates malignant phenotype and paclitaxel resistance in breast cancer cells via targeting the
Zhihua Kong1, Qi Han2, Bisheng Zhu2
1Department of Ultrasound, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning City, China.
Background:
Breast cancer is one of the most malignant cancers. Increasing evidence suggests that circular RNAs (circRNAs) are involved in breast cancer progression through sponging microRNA (miRNA). However, the underlying molecular mechanisms of circ_0069094 in breast cancer are unclear. This study aimed to reveal the effect of the circ_0069094/miR-136-5p/tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) pathway on the malignant progression of breast cancer.
Methods:
The quantitative real-time polymerase chain reaction and western blot were used to assess the expression of circRNA/miRNA/mRNA. The functional effects of circ_0069094 on the cell processes of breast cancer were investigated by cell counting kit-8, colony-forming assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and transwell invasion assay. The interactions among circ_0069094, miR-136-5p, and YWHAZ were assessed by dual-luciferase reporter assay. A xenograft experiment was performed to determine the effects of circ_0069094 on tumor formation.
Results:
Circ_0069094 was overexpressed in paclitaxel (PTX)-resistant breast cancer tissues and cells, and the silencing of circ_0069094 decreased tumor growth, cell proliferation and cell invasion while increasing PTX sensitivity and cell apoptosis in PTX-resistant cells. In addition, miR-136-5p was a target of circ_0069094, and miR-136-5p inhibition abolished circ_0069094 knockdown-induced effects in PTX-resistant cells. MiR-136-5p expression was decreased in PTX-resistant breast cancer tissues and cells, and the overexpression of miR-136-5p suppressed the malignant behaviors of breast cancer cells by targeting YWHAZ. Importantly, circ_0069094 regulated YWHAZ expression in breast cancer by targeting miR-136-5p.
Conclusion:
Circ_0069094 silencing improved PTX sensitivity in breast cancer progression through competitively sponging miR-136-5p.
Insights
Silencing circ_0069094 enhances paclitaxel sensitivity in breast cancer by sponging miR-136-5p. This circRNA pathway impacts tumor progression and chemoresistance in breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a leading cause of cancer mortality.
- Circular RNAs (circRNAs) are implicated in cancer progression, often by interacting with microRNAs (miRNAs).
- The specific role of circ_0069094 in breast cancer remains largely unknown.
Purpose of the Study:
- To investigate the molecular mechanism of circ_0069094 in breast cancer progression.
- To elucidate the role of the circ_0069094/miR-136-5p/YWHAZ pathway in malignant behaviors of breast cancer.
- To assess the impact of circ_0069094 on paclitaxel (PTX) resistance.
Main Methods:
- Quantitative real-time PCR and Western blot to measure circRNA, miRNA, and mRNA expression.
- Cell proliferation, invasion, apoptosis, and chemo-sensitivity assays (CCK-8, colony formation, EdU, flow cytometry, transwell).
- Dual-luciferase reporter assays and xenograft experiments to confirm molecular interactions and in vivo effects.
Main Results:
- Circ_0069094 was upregulated in PTX-resistant breast cancer tissues and cells.
- Silencing circ_0069094 inhibited proliferation and invasion, increased apoptosis, and enhanced PTX sensitivity.
- Circ_0069094 acts as a sponge for miR-136-5p, which targets YWHAZ, thus regulating breast cancer progression.
Conclusions:
- Circ_0069094 silencing improves PTX sensitivity in breast cancer progression.
- The circ_0069094/miR-136-5p/YWHAZ axis is a key regulator of breast cancer malignancy and chemoresistance.
- Targeting circ_0069094 may represent a therapeutic strategy for PTX-resistant breast cancer.
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