title: MicroRNA-148a inhibits migration and invasion of ovarian cancer cells via targeting sphingosine-1-phosphate receptor 1.
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.
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Zhengfang
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Shaoru
authors.initials: S
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D049349:Receptors, Lysosphingolipid / Q000235:genetics*; D000081025:Sphingosine-1-Phosphate Receptors; D015854:Up-Regulation
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors