title: A single nucleotide variant in microRNA-1269a promotes the occurrence and process of hepatocellular carcinoma by targeting to oncogenes SPATS2L and LRP6.
abstract: Hepatocellular carcinoma (HCC) is one of the malignant and lethal cancers. Single nucleotide polymorphisms (SNPs) in microRNAs(miRNAs) can affect the expression and target identification of miRNAs and lead to the formation of malignant tumors. However, little is known about whether microRNA-1269a (miR-1269a) SNPs affect the susceptibility and progression of HCC or their specific mechanism. The association between microRNA-1269a rs73239138 and the susceptibility to HCC was verified by MassARRAY assay in a large case-control sample. The effect of miR-1269a and the variant on the proliferation and apoptosis of HCC cells was examined by flow cytometry (FCM), CCK8 assay and Western blot. The target of miR-1269a was identified by bioinformatics analysis and qRT-PCR and its role on cell proliferative capacity was examined by CCK8 assay. The expression level of miR-1269a was analyzed by qRT-PCR in HCC cells transfected with wild or variant type pre-miR-1269a plasmid.MiR-1269a produced a tumor suppressor effect by inhibiting cell proliferation and inducing apoptosis of human HCC cells, possibly via inhibiting the expression of its target genes SPATS2L and LRP6, which were tumor promoters. While, rs73239138 (G>A) in miR-1269a reduced the anticancer effect of miR-1269a possibly by attenuating its total amount in HCC cells or its target recognition, reduce its inhibition on target genes and promoted the susceptibility to HCC. Our findings for the first time proved that miR-1269a SNP plays a role in the occurrence and process of HCC and the relevant mechanism, in accompany with the discovery of the novel target genes of miR-1269a.
authors.affiliation: Xiamen University, Southeast Hospital, Department of Digestive Diseases, Zhangzhou, Fujian, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Min
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Wenshuai
authors.initials: W
authors.lastname: Li
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Deqing
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Diannan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Wanwei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Fudan University, Huashan Hospital, Department of Pathology, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.affiliation: Fudan University, Huashan Hospital, Department of Laboratory Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Fudan University, Pudong Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Shi
authors.affiliation: Second Military Medical University, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Hu
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Dongqin
authors.initials: D
authors.lastname: Yang
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Fudan University, Huashan Hospital, Department of Digestive Diseases, Shanghai, China. Electronic address: archsteed@gmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Xiamen University, Southeast Hospital, Department of Digestive Diseases, Zhangzhou, Fujian, China. Electronic address: Zhangmq8084@hotmail.com.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009857:Oncogenes; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C000600169:MIRN1269 microRNA, human; D035683:MicroRNAs; D011506:Proteins; C582423:SPATS2L protein, human
keywords: Hepatocellular carcinoma; LRP6; SPATS2L; hepatocellular carcinoma; miR-1269a; rs73239138