Circ_0014130通过miR-197-3p/PFKFB3轴参与结直肠癌的药物敏感性。
Circ_0014130 is involved in the drug sensitivity of colorectal cancer through miR-197-3p/PFKFB3 axis.
作者信息
Wang Wei, Zhou Lijiang, Li Zheng, Lin Guanhong
机构信息
Department of Integrated Traditional Chinese and Western Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China.
Department of Oncology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
出版信息
J Gastroenterol Hepatol. 2022 May;37(5):908-918. doi: 10.1111/jgh.15829. Epub 2022 Mar 28.
BACKGROUND AND AIM
Colorectal cancer (CRC) is one of the most deadly cancers in the world, with few treatments and a poor prognosis. In recent years, many circular RNAs have been studied in CRC, but the role of circ_0014130 in CRC has not been investigated. Therefore, this research is designed to investigate the impact of circ_0014130 on the resistance of 5-fluorouracil (5-FU) in CRC.
METHODS
Quantitative real-time polymerase chain reaction was conducted to assess the expression of circ_0014130, microRNA-197-3p (miR-197-3p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3). The expression of PFKFB3 protein was detected by Western blot. The effect of cric_0014130 on drug resistance in CRC was verified by Cell Counting Kit-8 assay, clone formation assay, Transwell, and flow cytometry. The effect of circ_0014130 on tumor growth was evaluated by xenograft tumor model in vivo.
RESULTS
Circ_0014130 and PFKFB3 were increased, while miR-197-3p was reversed in CRC tissues and cells. Knocking down circ_0014130 can promote cell apoptosis, inhibit the proliferation of CRC cells, and reduced the IC50 of 5-FU. In addition, miR-197-3p inhibitors reversed the effect of si-circ_0014130 on CRC cells. Similarly, overexpression of PFKFB3 can regulate CRC cell behavior and 5-FU resistance caused by miR-197-3p. Finally, decrease of circ_0014130 was demonstrated to enhance the resistance of 5-FU in CRC tissues in vivo.
CONCLUSION
Circ_0014130 modulates 5-FU resistance in CRC by modulating the miR-197-3p/PFKFB3 axis, which is helpful for drug chemotherapy in CRC.
背景与目的
结直肠癌（CRC）是全球最致命的癌症之一，治疗手段有限且预后较差。近年来，许多环状RNA在结直肠癌中得到研究，但circ_0014130在结直肠癌中的作用尚未被探究。因此，本研究旨在探讨circ_0014130对结直肠癌中5-氟尿嘧啶（5-FU）耐药性的影响。
方法
采用定量实时聚合酶链反应评估circ_0014130、微小RNA-197-3p（miR-197-3p）和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3（PFKFB3）的表达。通过蛋白质印迹法检测PFKFB3蛋白的表达。采用细胞计数试剂盒-8法、克隆形成试验、Transwell实验和流式细胞术验证circ_0014130对结直肠癌耐药性的影响。通过体内异种移植肿瘤模型评估circ_0014130对肿瘤生长的影响。
结果
在结直肠癌组织和细胞中，circ_0014130和PFKFB3表达上调，而miR-197-3p表达下调。敲低circ_0014130可促进细胞凋亡，抑制结直肠癌细胞增殖，并降低5-FU的半数抑制浓度（IC50）。此外，miR-197-3p抑制剂可逆转si-circ_0014130对结直肠癌细胞的作用。同样，PFKFB3的过表达可调节结直肠癌细胞行为以及由miR-197-3p引起的5-FU耐药性。最后，体内实验证明circ_0014130的降低可增强结直肠癌组织对5-FU的耐药性。
结论
circ_0014130通过调节miR-197-3p/PFKFB3轴调控结直肠癌对5-FU的耐药性，这对结直肠癌的药物化疗有帮助。
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