The M6A methyltransferase METTL3: acting as a tumor suppressor in renal cell carcinoma
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Xiao Li1,2,*, Jingyuan Tang1,3,*, Wen Huang4,*, Feng Wang1, Pu Li1, Chao Qin1, Zhiqiang Qin1, Qing Zou2, Jifu Wei4, Lixin Hua1, Haiwei Yang1 and Zengjun Wang1
1State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2Department of Urology, Affiliated Cancer Hospital of Jiangsu Province of Nanjing Medical University, Nanjing 210009, China
3Department of Urology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing 210029,China
4Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
*These authors have contributed equally to this work
Haiwei Yang, email: firstname.lastname@example.org
Jifu Wei, email: email@example.com
Lixin Hua, email: firstname.lastname@example.org
Keywords: methyltransferase; METTL3; renal cell carcinoma
Received: February 14, 2017 Accepted: July 25, 2017 Published: October 10, 2017
We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis and development. Immunohistochemistry was performed in clinical tissue microarray. Expression level of METTL3 in RCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the effects of METTL3 on proliferation, migration, invasion and cell cycle were studied in RCC cells. Additionally, in vivo study was carried out in nude mice. Negative METTL3 expression was associated with larger tumor size (P=0.010) and higher histological grade (P=0.021). Moreover, RCC patients with positive METTL3 expression had an obvious longer survival time (P=0.039). METTL3 mRNA and protein expression was lower in RCC samples compared with adjacent non-tumor samples, and lower in RCC cell lines (CAKI-1, CAKI-2 and ACHN) compared with HK-2. Afterwards, knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest. In contrast, up-regulation of METTL3 could inhibit such functions and reduce G0/G1 arrest. Additionally, up-regulation of METTL3 significantly suppressed tumor growth in vivo. Furthermore, significant changes in epithelial-to-mesenchymal transition (EMT) and PI3K-Akt-mTOR pathways were observed. Overall, our findings demonstrated that METTL3 might have a carcinostasis role in cell proliferation, migration, invasion function and cell cycle of RCC, indicating METTL3 may act as a novel marker for tumorigenesis, development and survival of RCC.
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