Methylation-associated silencing of miR-638 promotes endometrial carcinoma progression by targeting MEF2C
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Authors: Ni, Jianjiao; Liang, Shanhui; Shan, Boer; Tian, Wenjuan; Wang, Huaying; Ren, Yulan
Abstract
Promoter methylation-associated silencing of cancer-associated microRNAs (miRNAs) is a common epigenetic mechanism during tumorigenesis in various types of human cancer. However, this has not been comprehensively examined in endometrial carcinoma (EC). In the present study, an miRNA microarray consisting of 1,347 common human miRNAs was used to select potential tumor suppressive miRNAs that were hyper-methylated in EC. This led to the identification of miR-638, miR-210 and miR-3665. The methylation status of miR-638 was examined by bisulfite sequencing polymerase chain reaction and miR-638 expression was measured by TaqMan miRNA assays. EC cell lines transfected with vectors overexpressing miR-638, its target gene myocyte enhancer factor 2C (MEF2C) or both, were constructed. Dual-luciferase reporter assays, a xenograft mouse model and rescue experiments were designed to study miR-638 and its target gene MEF2C. The results indicated that the promoter region of miR-638 was highly methylated and the expression of miR-638 was significantly downregulated in cancerous tissues from 42 patients with EC who underwent surgical resection. Additionally, a low expression of miR-638 was significantly associated with advanced Federation of Gynecology and Obstetrics stage and was demonstrated to indicate shorter disease-free survival. Functional studies indicated that the overexpression of miR-638 in EC cell lines inhibited in vitro tumor progression and in vivo tumorigenicity. MEF2C was verified as a direct target of miR-638 and was demonstrated to mediate the tumor-suppressive function of miR-638 in EC.
Genome-Wide Analysis Reveals Changes in Polled Yak Long Non-coding RNAs in Skeletal Muscle Development
FRONTIERS IN GENETICS
Authors: Ma, Xiaoming; Fu, Donghai; Chu, Min; Ding, Xuezhi; Wu, Xiaoyun; Guo, Xian; Kalwar, Qudratullah; Pei, Jie; Bao, Pengjia; Liang, Chunnian; Yan, Ping
Abstract
Long non-coding RNAs (lncRNAs) have been extensively studied in recent years. Numerous lncRNAs have been identified in mice, rats, and humans, some of which play important roles in muscle formation and development. However, little is known about lncRNA regulators that affect muscle development in yak (Bos grunniens). LncRNA expression during skeletal muscle development in yak was analyzed by RNA sequencing at three development stages: 3 years (group A), 6 months (group M), and 90-day-old fetuses (group E). A total of 1180 lncRNAs were identified in the three development stages. Compared with group E, 154 were upregulated and 130 were downregulated in group A. Compared with group A, 31 were upregulated and 29 were downregulated in group M. Compared with group E, 147 were upregulated and 149 were downregulated in group M (padj < 0.001, |log2FC| > 1.2). In addition, functional annotation analysis based on gene ontology (GO) and the Kyoto protocol encyclopedia of genes and genomes (KEGG) database showed that differentially expressed lncRNAs (DElncRNAs) were cis-trans target genes. The results showed that DElncRNAs were mainly involved in PI3K-Akt signaling pathway, focal adhesion, MAPK signaling pathway, apoptosis, and p53 signaling pathway. Furthermore, RTL1, IGF2, MEF2C, Pax7, and other well-known muscle development regulators were included in a co-expression network of differentially expressed target genes and lncRNAs. These data will help to further clarify the function of lncRNAs in the different stages of skeletal muscle developmental in yak.