PKM2 functions as a potential oncogene and is a crucial target of miR-148a and miR-326 in thyroid tumorigenesis

American Journal of Translational Research

Gang Yu¹  Weili Sun² 

[1] Department of General Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, China;Department of Nuclear Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China

关键词: PKM2;    thyroid cancer;    miR-148a;    miR-326;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

In this study, we investigated the biological function of pyruvate kinase M2 (PKM2) and its regulation by deregulated microRNAs (miRNAs) in thyroid cancer (TC). The mRNA and protein expression of PKM2 was examined by quantitative reverse transcription PCR and western blot. The biological role of PKM2 was demonstrated through small interfering RNA-mediated knockdown experiments. The regulation of PKM2 by miR-148a and miR-326 was confirmed by western blot, dual luciferase activity assays, and rescue experiments. PKM2 was overexpressed in TC tissues and cell lines. The knockdown of PKM2 in TC cells suppressed cell proliferation, reduced colony formation, and inhibited cell invasion and migration significantly. Luciferase reporter assays revealed that PKM2 is a direct target of two tumor-suppressive miRNAs, miR-148a and miR-326. Re-expressed PKM2 rescued the anticancer effects of miR-148a. Taken together, these data strongly suggest that, apart from gene amplification and mutation, the activation of PKM2 in TC is partly due to the down-regulation of the tumor-suppressive miRNAs miR-148a and miR-326. Thus, PKM2 is overexpressed and plays an oncogenic role in thyroid carcinogenesis.

【 授权许可】

CC BY-NC