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Chaperon‑mediated autophagy can promote proliferation and invasion of renal carcinoma cells and inhibit apoptosis through PKM2.
Oncology Reports ( IF 3.8 ) Pub Date : 2021-08-09 , DOI: 10.3892/or.2021.8165
Shangwen Xiao 1 , Gang Xu 2 , Zhenlong Wang 3 , Tie Chong 3
Affiliation  

The aim of the present study was to explore the effect of chaperon‑mediated autophagy (CMA) through pyruvate kinase isoform M2 (PKM2) on the development of renal carcinoma (RCC) and its possible mechanisms. Lysosome‑associated membrane protein 2A (LAMP‑2A) and PKM2 expression levels were detected by collecting tissue samples from RCC patients. RNA interference was used to silence the LAMP‑2A and PKM2 expression levels in renal cell line A498 to detect the proliferation, apoptosis and invasion of cells. The levels of mRNA and protein of related genes were also examined. Co‑immunoprecipitation was used to detect the interaction between PKM2 and heat shock cognate 70 (HSC70). The results revealed that LAMP‑2A and PKM2 expression levels were significantly increased in RCC tissues and cell lines (P<0.01). LAMP‑2A silencing increased the expression level of PKM2 in A498 and 786‑O cells. LAMP‑2A and PKM2 silencing suppressed the proliferation and invasion and induced the apoptosis of A498 cells, and also affected the expression levels of related genes. Co‑immunoprecipitation revealed the interaction between PKM2 and HSC70. In conclusion, CMA could affect the proliferation, invasion and apoptosis of RCC cells through PKM2, and our findings provided new biomarkers and targets for molecular targeted therapy of RCC.

中文翻译:


伴侣介导的自噬可以促进肾癌细胞的增殖和侵袭,并通过 PKM2 抑制细胞凋亡。



本研究的目的是探讨通过丙酮酸激酶同工型M2(PKM2)进行伴侣介导的自噬(CMA)对肾癌(RCC)发生发展的影响及其可能的机制。通过收集肾细胞癌患者的组织样本来检测溶酶体相关膜蛋白 2A (LAMP-2A) 和 PKM2 的表达水平。采用RNA干扰技术沉默肾细胞系A498中LAMP-2A和PKM2的表达水平,检测细胞的增殖、凋亡和侵袭情况。还检测了相关基因的mRNA和蛋白质水平。免疫共沉淀用于检测 PKM2 和热休克同源 70 (HSC70) 之间的相互作用。结果显示,RCC组织和细胞系中LAMP-2A和PKM2表达水平显着升高(P<0.01)。 LAMP-2A 沉默增加了 A498 和 786-O 细胞中 PKM2 的表达水平。 LAMP-2A和PKM2沉默可抑制A498细胞的增殖和侵袭并诱导其凋亡,并影响相关基因的表达水平。免疫共沉淀揭示了 PKM2 和 HSC70 之间的相互作用。总之,CMA可以通过PKM2影响RCC细胞的增殖、侵袭和凋亡,我们的研究结果为RCC分子靶向治疗提供了新的生物标志物和靶点。
更新日期:2021-08-09
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