Long non-coding RNA ELF3-antisense RNA 1 promotes osteosarcoma cell proliferation by upregulating Kruppel-like factor 12 potentially via methylation of the microRNA-205 gene
ONCOLOGY LETTERS
Authors: Yuan, Jianmin; Kang, Jianhui; Yang, Min
Abstract
A recent study characterized the long non-coding RNA (lncRNA) ELF3-antisense RNA 1 (ELF3-AS1) as an oncogenic lncRNA in bladder cancer. The present study aimed to investigate the role of ELF3-AS1 in osteosarcoma (OS). It was found that ELF3-AS1 was upregulated in OS tissues, and ELF3-AS1 expression level increased with increasing clinical stage. In OS tissues, Kruppel-like factor 12 (KLF12) was positively correlated with ELF3-AS1, while microRNA (miR)-205 was negatively correlated with ELF3-AS1. ELF3-AS1 overexpression resulted in the upregulation of KLF12, but the downregulation of miR-205. Overexpression of miR-205 caused downregulation of KLF12, but had no significant effects on ELF3-AS1 expression. Overexpression of KLF12 showed no significant impact on ELF3-AS1 and miR-205. ELF3-AS1 and KLF12 overexpression resulted in an increased proliferation rate in OS cells, while miR-205 played an opposite role and attenuated the effects of ELF3-AS1 overexpression. ELF3-AS1 overexpression promoted the methylation of the miR-205 gene. Therefore, ELF3-AS1 may promote OS cell proliferation by upregulating KLF12 through the methylation of the miR-205 gene.
Targeted re-sequencing of linkage region on 2q21 identifies a novel functional variant for hip and knee osteoarthritis
OSTEOARTHRITIS AND CARTILAGE
Authors: Taipale, M.; Jakkula, E.; Kamarainen, O. -P; Gao, P.; Skarp, S.; Barral, S.; Kiviranta, I.; Kroger, H.; Ott, J.; Wei, G. -H.; Ala-Kokko, L.; Mannikko, M.
Abstract
Objective: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families. Methods: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score. In addition, exome sequencing was performed in three family members from the same family. Results: Genome wide linkage analysis identified a susceptibility locus on chromosome 2q21 with a multipoint LOD score of 3.91. Targeted re-sequencing and subsequent linkage analysis revealed a susceptibility insertion variant rs11446594. It locates in a predicted strong enhancer element region with maximum LOD score 3.42 under dominant model of inheritance. Insertion creates a recognition sequence for ELF3 and HMGA1 transcription factors. Their DNA-binding affinity is highly increased in the presence of A-allele compared to wild type null allele. Conclusion: A potentially novel functional OA susceptibility variant was identified by targeted resequencing. This variant locates in a predicted regulatory site and creates a recognition sequence for ELF3 and HMGA1 transcription factors that are predicted to play a significant role in articular cartilage homeostasis. (C) 2015 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.
COA
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