Upregulated microRNA‐15b alleviates ovarian cancer through inhitbition of the PI3K/Akt pathway by targeting LPAR3
Authors: Xu-Ling Qin
Yong-Sheng Wang
Jun-Ling Gong
Huai-Hua Song
Ying-Ni Li
Guang-Cai Li
Yu-Yan Qiu
Hui Wang
Shi-Chang Cui
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: LPAR3; PI3K/Akt pathway; apoptosis; microRNA-15b; ovarian cancer
Affiliations: Department of Obstetrics and Gynecology Linyi People's Hospital Linyi People's Republic of China, Department of Emergency Economic and Technological Development Zone People's Hospital of Linyi Linyi People's Republic of China, Department of Obstetrics and Gynecology The Third People's Hospital of Linyi Linyi People's Republic of China, Department of Obstetrics and Gynecology Economic and Technological Development Zone People's Hospital of Linyi Linyi People's Republic of China, Department of General Surgery Linyi Central Hospital Linyi People's Republic of China

Abstract:  Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b. 

Retracted: Yes

PubPeer comments:
 Fig 5(d).  Cell cycle distribution in response to miRu201015b mimic, miRu201015b inhibitor, siRNAu2010LPAR3, and miRu201015b inhibitor + siRNAu2010LPAR3 measured by flow cytometry . ![file] Overhangs in the cell-count histogram. Inquiring minds are wondering about the software and hardware used for plotting. Figs 4(b), 2(d), 3(b). ![file] I am intrigued by the absence of background on these WBs, and the way the bands remain perfectly linear and retain the shape of the protein blobs as they move up the gel. Is it possible for the authors to upload the original scans of the gels? Numerous other papers have Figures which display the same qualities, hence my curiosity. I compiled a montage: ![] , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 29 May 2019 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. As several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. ,