Abstract
BackgroundCircular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer.MethodsThirty nine paired breast cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast cancer tumor growth in vivo was analyzed via xenograft model.ResultscircFBXL5 was highly expressed in breast cancer tissues and cells, and was more upregulated in 5-FU-resistant breast cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast cancer by inhibiting cell migration, invasion and promoting apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast cancer. Furthermore, circFBXL5 interference declined breast cancer tumor growth in xenograft model.ConclusionOur data showed that circFBXL5 could promote the 5-FU resistance of breast cancer by regulating miR-216b/HMGA2 axis.
Highlights
Breast cancer is one common malignant cancer in women [1]. 5-fluorouracil (5-FU) is an antitumor agent via affecting pyrimidine synthesis, which is applied toThe noncoding RNAs are relevant to various events of breast cancer progression [3]
Our study aims to explore the role of circFBXL5 in the 5-FU resistance of breast cancer
Results circFBXL5 abundance is elevated in breast cancer To explore whether circFBXL5 was implicated in breast cancer progression, we collected 39 paired breast cancer tissues and normal tissues, and measured circFBXL5 expression
Summary
The noncoding RNAs are relevant to various events of breast cancer progression [3]. CircRNA CDR1as knockdown repressed 5-FU resistance in breast cancer cells via regulating miR-7 [8]. Studies had shown that circFBXL5 was associated with the poor prognosis in breast cancer patients, which could facilitate cancer progression via modulating miR-660 [9]. Whether circFBXL5 are involved in the regulation of 5-FU resistance in breast cancer remain unknown. Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. How and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer
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