MicroRNA-148a inhibits migration and invasion of ovarian cancer cells via targeting sphingosine-1-phosphate receptor 1
MOLECULAR MEDICINE REPORTS
Authors: Wen, Zhengfang; Zhao, Shuzhen; Liu, Shanshan; Liu, Ying; Li, Xiaorui; Li, Shaoru
Abstract
MicroRNAs, a group of small non-coding RNA molecules that are involved in gene silencing, function as fine-tuning regulators during cancer progression. MicroRNA (miR)-148a has previously been demonstrated to be associated with ovarian cancer. However, whether miR-148a influences the migration and invasion of ovarian cancer cells has remained elusive. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were conducted to examine mRNA and protein expression levels, respectively. Luciferase reporter assay was used to determine target relationship, and a Transwell assay was used to study cell migration and invasion. The results of the present study indicated that miR-148a expression was markedly downregulated in ovarian cancer tissues compared with that of their matched normal adjacent tissues. In addition, miR-148a expression levels were reduced in three ovarian cancer cell lines, SKOV3, OVCAR and A2780, when compared with those of HUM-CELL-0088 normal ovarian epithelial cells. Furthermore, sphingosine-1-phosphate receptor 1 (S1PR1), which is upregulated in ovarian cancer tissues and cell lines, was identified as a novel target of miR-148a in SKOV3 ovarian cancer cells. The protein expression of S1PR1 was negatively regulated by miR-148a in SKOV3 cells. Furthermore, overexpression of miR-148a or inhibition of S1PR1 suppressed SKOV3 cell migration and invasion, while restoration of S1PR1 expression reversed the suppressive effect of miR-148a upregulation on SKOV3 cell migration and invasion. In conclusion, it was hypothesized that miR-148a may potentially be used as a molecular agent for the prevention and treatment of invasion and metastasis in ovarian cancer, while S1PR1 may present a promising target for clinical applications.
Identification of Recently Selected Mutations Driven by Artificial Selection in Hanwoo (Korean Cattle)
ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES
Authors: Lim, Dajeong; Gondro, Cedric; Park, Hye Sun; Cho, Yong Min; Chai, Han Ha; Seong, Hwan Hoo; Yang, Bo Suk; Hong, Seong Koo; Chang, Won Kyung; Lee, Seung Hwan
Abstract
Hanwoo have been subjected over the last seventy years to intensive artificial selection with the aim of improving meat production traits such as marbling and carcass weight. In this study, we performed a signature of selection analysis to identify recent positive selected regions driven by a long-term artificial selection process called a breeding program using whole genome SNP data. In order to investigate homozygous regions across the genome, we estimated iES (integrated Extended Haplotype Homozygosity SNP) for the each SNPs. As a result, we identified two highly homozygous regions that seem to be strong and/or recent positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN) were included in this region. To go further in the interpretation of the observed signatures of selection, we subsequently concentrated on the annotation of differentiated genes defined according to the iES value of SNPs localized close or within them. We also described the detection of the adaptive evolution at the molecular level for the genes of interest. As a result, this analysis also led to the identification of OLFM3 as having a strong signal of selection in bovine lineage. The results of this study indicate that artificial selection which might have targeted most of these genes was mainly oriented towards improvement of meat production.