Chen Yuan Yuan, Luo Li Ping, Deng Ke Chong
Department of Oncology, Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, 430063, China.
Department of Emergency, Wuhan Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, 430063, China.
Acta Biochim Pol. 2023 Mar 17;70(1):153-162. doi: 10.18388/abp.2020_6379.
A great many circular RNAs (circRNAs) are considered key modulators of human malignancies. However, the function of circRNA lysophosphatidic acid receptor 3 (LPAR3) in the radioresistance of prostate cancer (PCa) cells is still uncertain. circLPAR3, microRNA (miR)-329-3p, and JPT1 expression in PCa tissues and cells were detected by real-time quantitative PCR or western blot. Cell proliferation was detected by CCK-8 (cell proliferation assay) and colony formation assay, apoptosis was by flow cytometry, and migration and invasion ability were by Transwell assay. Cell glycolysis was analyzed by glucose uptake, lactate production, and ATP metabolism. Under different doses of radiation, the radiosensitivity of PCa cells was detected by colony formation assay. The relationship between circLPAR3, miR-513b-5p, and JPT1 was confirmed by dual luciferase reporter gene detection and RIP assay. The data presented that circLPAR3 and JPT1 expression was elevated in PCa, while miR-513b-5p expression was reduced. Repression of circLPAR3 depressed cell advancement, and restrained glycolysis, but enhanced the radiosensitivity of PCa cells. CircLPAR3's target miRNA was miR-513b-5p which targeted JPT1. Elevated JPT1 reversed the repressive effects of circLPAR3 knockdown or miR-513b-5p overexpression on PCa advancement, glycolysis, and radiosensitivity. In summary, the knockdown of circLPAR3 reduces glycolysis, but promotes PCa radiosensitivity via the miR-513b-5p/JPT1 axis, discovering a novel mechanism in PCa progression.
大量环状RNA(circRNA)被认为是人类恶性肿瘤的关键调节因子。然而,环状RNA溶血磷脂酸受体3(LPAR3)在前列腺癌(PCa)细胞放射抗性中的作用仍不明确。通过实时定量PCR或蛋白质免疫印迹法检测PCa组织和细胞中环状LPAR3、微小RNA(miR)-329-3p和JPT1的表达。通过CCK-8(细胞增殖检测)和集落形成试验检测细胞增殖,通过流式细胞术检测细胞凋亡,通过Transwell试验检测细胞迁移和侵袭能力。通过葡萄糖摄取、乳酸生成和ATP代谢分析细胞糖酵解。在不同剂量辐射下,通过集落形成试验检测PCa细胞的放射敏感性。通过双荧光素酶报告基因检测和RNA免疫沉淀试验(RIP)证实环状LPAR3、miR-513b-5p和JPT1之间的关系。数据表明,环状LPAR3和JPT1在PCa中的表达升高,而miR-513b-5p的表达降低。抑制环状LPAR3可抑制细胞进展,抑制糖酵解,但增强PCa细胞的放射敏感性。环状LPAR3的靶标微小RNA是miR-513b-5p,其靶向JPT1。JPT1表达升高可逆转环状LPAR3敲低或miR-513b-5p过表达对PCa进展、糖酵解和放射敏感性的抑制作用。总之,环状LPAR3的敲低可减少糖酵解,但通过miR-513b-5p/JPT1轴促进PCa的放射敏感性,揭示了PCa进展中的一种新机制。