title: MiR-33a suppresses proliferation of NSCLC cells via targeting METTL3 mRNA.
abstract: Methyltransferase like 3 (METTL3) was incipiently known as a methyltransferase which was responsible for N6-methyladenosine (m6A) methylation. METTL3 can promote the expression of several crucial oncoproteins and its high expression enhanced proliferation, survival, and invasion of human lung cancer cells. However, how METTL3 was regulated is seldom understood in non-small-cell lung carcinoma (NSCLC). In the present study, miR-33a was suspicious to target to the 3'-untranslated region (3'UTR) of METTL3 mRNA via in silico prediction. Besides, the expressions of METTL3 were higher in NSCLC tissues than those in adjacent tissues, and METTL3 expressions were positively related to the expressions of miR-33a in NSCLC tissues which confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-33a can directly target to the 3'UTR of METTL3 mRNA which examined by luciferase reporter gene assay. Moreover, we found that miR-33a can reduce the expression of METTL3 at both mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Functionally, miR-33a can reduce the proliferation of A549 and NCI-H460 cells. Conversely, inhibition of miR-33a by anti-miR-33a can rescue that using 4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2-deoxyuridine (EdU) assay. Similarly, miR-33a can reduce cellular anchorage-independent growth of A549 cells. Additionally, the negative influences of miR-33a on the downstream genes of METTL3 were examined by Western blot analysis. Thus, we concluded that miR-33a can attenuate NSCLC cells proliferation via targeting to the 3'UTR of METTL3 mRNA. Our findings provide new insights into the mechanism of METTL3 regulation by micro RNA, and supports METTL3 as a therapeutic target in NSCLC.
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Juwei
authors.initials: J
authors.lastname: Mou
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Shugeng
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. Electronic address: gaoyushun1027@163.com.
authors.forename: Yushun
authors.initials: Y
authors.lastname: Gao
mesh_terms: D020413:3' Untranslated Regions; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008780:Methyltransferases / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008780:Methyltransferases; C468275:METTL3 protein, human
keywords: EGFR; METTL3; NSCLC; Proliferation; miR-33a