HNRNPC Regulates GLUT1/LDHA Pathway by Stabilizing FOXM1 mRNA to Promote the Progression and Aerobic Glycolysis of Multiple Myeloma.

IF 1.1 4区 医学 Q4 MEDICAL LABORATORY TECHNOLOGY
Ningning Wu, Yao Zhu
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引用次数: 0

Abstract

Objective: Multiple Myeloma (MM) is a malignant hematological disease. Heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) acts as an oncogene in a variety of cancers. However, the role of HNRNPC in MM has not been reported so far.

Methods: The mRNA and protein expressions of HNRN-PC and FOXM1 were detected by qRT-PCR and western blot. CCK8, EDU staining, flow cytometry and western blot were used to detect cell viability and cell cycle. The extracellular flux analyzer XF96 was used to detect the production of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Lactic acid and glucose levels in culture medium were detected by lactic acid assay kits and glucose assay kits, respectively. Then, the binding ability of HNRNPC with FOXM1 was detected by RIP and the stability of FOXM1 mRNA was appraised with qRT-PCR. With the application of qRT-PCR and western blot, the transfection efficacy of si-HNRNPC and Oe-FOXM1 was examined. Western blot was applied for the estimation of GLUT1/LDHA signaling pathway-related proteins.

Results: The expression of HNRNPC in MM cell line was abnormally elevated. HNRNPC silence significantly inhibited the proliferation, facilitated the apoptosis, induced cycle arrest, and suppressed aerobic glycolysis in MM cells, which were all reversed by FOXM1 overexpression. It was also found that the regulatory effect of HNRNPC is realized by stabilizing FOXM1 mRNA and regulating GLUT1/LDHA pathway.

Conclusion: HNRNPC regulated GLUT1/LDHA pathway by stabilizing FOXM1 mRNA to promote the progression and aerobic glycolysis of MM.

HNRNPC 通过稳定 FOXM1 mRNA 来调控 GLUT1/LDHA 通路,从而促进多发性骨髓瘤的进展和有氧糖酵解。
目的:多发性骨髓瘤(MM)是一种恶性血液病:多发性骨髓瘤(MM)是一种恶性血液病。异质核糖核蛋白 C1/C2 (HNRNPC)是多种癌症的致癌基因。然而,迄今为止,HNRNPC在MM中的作用尚未见报道:方法:通过qRT-PCR和Western blot检测HNRN-PC和FOXM1的mRNA和蛋白表达。采用 CCK8、EDU 染色、流式细胞术和 western 印迹检测细胞活力和细胞周期。细胞外通量分析仪 XF96 用于检测耗氧率(OCR)和细胞外酸化率(ECAR)的产生。乳酸检测试剂盒和葡萄糖检测试剂盒分别检测培养液中的乳酸和葡萄糖含量。然后,用 RIP 检测 HNRNPC 与 FOXM1 的结合能力,并用 qRT-PCR 评估 FOXM1 mRNA 的稳定性。应用qRT-PCR和Western blot检测了si-HNRNPC和Oe-FOXM1的转染效果。Western blot用于评估GLUT1/LDHA信号通路相关蛋白:结果:HNRNPC在MM细胞系中的表达异常升高。结果:HNRNPC在MM细胞株中的表达异常升高,沉默的HNRNPC能明显抑制MM细胞的增殖、促进细胞凋亡、诱导细胞周期停滞和抑制有氧糖酵解,而FOXM1的过表达能逆转这些作用。研究还发现,HNRNPC的调控作用是通过稳定FOXM1 mRNA和调控GLUT1/LDHA通路实现的:结论:HNRNPC通过稳定FOXM1 mRNA来调控GLUT1/LDHA通路,从而促进MM的进展和有氧糖酵解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annals of clinical and laboratory science
Annals of clinical and laboratory science 医学-医学实验技术
CiteScore
1.60
自引率
0.00%
发文量
112
审稿时长
6-12 weeks
期刊介绍: The Annals of Clinical & Laboratory Science welcomes manuscripts that report research in clinical science, including pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.
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