Whole genome sequencing identifies ANXA3 and MTHFR mutations in a large family with an unknown equinus deformity associated genetic disorder
MOLECULAR BIOLOGY REPORTS
Authors: Zhang, Zhiqun; Kong, Zhuqing; Zhu, Miao; Lu, Wenxiang; Ni, Lei; Bai, Yunfei; Lou, Yue
Abstract
The aim of this study was to characterize a previously uncharacterized genetic disorder associated with equinus deformity in a large Chinese family at the genetic level. Blood samples were obtained and whole genome sequencing was performed. Differential gene variants were identified and potential impacts on protein structure were predicted. Based on the control sample, several diseases associated variants were identified and selected for further validation. One of the potential variants identified was a ANXA3 gene [chr4, c.C820T(p.R274*)] variant. Further bioinformatic analysis showed that the observed mutation could lead to a three-dimensional conformational change. Moreover, a MTHFR variant that is different from variants associated with clubfoot was also identified. Bioinformatic analysis showed that this mutation could alter the protein binding region. These findings imply that this uncharacterized genetic disorder is not clubfoot, despite sharing some similar symptoms. Furthermore, specific CNV profiles were identified in association with the diseased samples, thus further speaking to the complexity of this multigenerational disorder. This study examined a previously uncharacterized genetic disorder appearing similar to clubfoot and yet having distinct features. Following whole genome sequencing and comparative analysis, several differential gene variants were identified to enable a further distinction from clubfoot. It is hoped that these findings will provide further insight into this disorder and other similar disorders.
Lnc00908 promotes the development of ovarian cancer by regulating microRNA-495-5p
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Jiang, J-N; Hong, Q-Y; Gao, H-J; Lai, B-L; Lan, J-F; Yang, Q.
Abstract
OBJECTIVE: The aim of this study was to investigate whether Inc00908 could affect the proliferative and migratory behaviors of ovarian cancer (OC) cells by regulating microRNA-495-5p, thus participating in the development of OC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was used to detect the expression levels of Inc00908 and microRNA-495-5p in OC tissues and normal ovarian tissues, as well as OC cell lines. The regulatory effects of Inc00908 and microRNA-495-5p on the proliferative and migration abilities of OC cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. The binding relationship between microRNA-495-5p and ANXA3, as well as miR-495-5p and Inc00908, was examined by luciferase reporter gene assay. Gain-of-function experiments were conducted to verify whether Inc00908 could affect the proliferative and migratory behaviors of OC cells by regulating microRNA-495-5p. RESULTS: Lnc00908 was highly expressed in OC tissues, and its expression was positively correlated with tumor stage. Overexpression of Inc00908 markedly promoted the proliferative and migratory abilities of SKOV3 and OVCAR cells. Luciferase reporter gene assay showed that Inc00908 could bind to microRNA-495-5p. However, microRNA-495-5p was significantly down-regulated in OC tissues. Overexpression of microRNA-495-5p reversed the enhanced abilities of proliferation and migration in SKOV3 and OVCAR3 cells by Inc00908 overexpression. ANXA3 was a target gene of microRNA-495-5p. Moreover, overexpression of ANXA3 attenuated the inhibitory effect of miR-495-5p on the proliferative and migratory behaviors of SKOV3 and OVCAR3 cells. CONCLUSIONS: We found that the high expression of Inc00908 can promote the proliferation and migration abilities of OC cells through sponging microRNA-495-5p to regulate ANXA3 expression.