Long non-coding RNA PVT1-mediated miR-543/SERPINI1 axis plays a key role in the regulatory mechanism of ovarian cancer
Authors: Junbao Liu
Yahua Guo
Rui Qin
Chunmei Dai
Chong Qu
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PVT1; SERPINI1; miR-543; ovarian cancer.
Affiliations: Department of Neurosurgery, China-Japan Union Hopsital of Jilin University, Changchun City, Jilin Province, China, School Hospital, Changchun University of Chinese Medicine, Changchun City, Jilin Province, China, Department of Obstetrics and Gynaecology of the China-Japan Union Hospital of Jilin University, Changchun City, Jilin Province, China

Abstract:  Purpose: To investigate the regulation mechanism of long non-coding RNA (lncRNA) plasmocytoma variant translocation 1 (PVT1) in ovarian cancer (OC). Methods: The levels of PVT1, microRNA (miR)-543, serpin peptidase inhibitor-clade I (neuroserpin)-member 1 (SERPINI1) in OC tissues and OVCAR-3, A2780, TOV-112D of OC cell lines were detected by quantitative real-time PCR (qRT-PCR) and Western Blot (WB). Cell proliferation, migration, invasion, apoptosis and the regulatory relationship between genes and target genes were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell, flow cytometry and dual luciferase reporter (DLR). The OC patients were followed up for 5 years to analyze the relationship between PVT1 and 5-year overall survival (OS). Results: In contrast with miR-543, PVT1 and SERPINI1 were highly expressed in OC tissues and cell lines, and high levels of PVT1 were significantly associated with lower 5-year OS of patients. Down-regulating PVT1 not only inhibited the malignant proliferation, migration and invasion of OC cells, but promoted cell apoptosis. PVT1 regulated miR-543 in a targeted manner, and its overexpression could attenuate the anticancer effect of miR-543 on OC cells. In addition, miR-543 also directly targeted SERPINI1, and miR-543 knockdown weakened the inhibitory effect of down-regulated SERPINI1 on OC progression. Furthermore, we found that PVT1 acted as a competitive endogenous RNA to sponge miR-543, thereby regulating the expression of SERPINI1. Conclusion: PVT1 can mediate the molecular mechanism of OC by miR-543/SERPINI1 axis regulatory network, which is a new therapeutic direction for OC. 

Retracted: No

PubPeer comments:
 Figure 1b. Much more similar and different than expected. ![file] , 
 Figure 6a. Much more similar than expected. ![file] , 
 #1 Publication of the two cited papers dates back to the year 2005. As can be easily seen by digital adjustments (contrast, brightness) the Western blots shown in the right panel (shows Figure 1b from Hemmati et al., Oncogene 2005) are uncut, i.e. in one piece. As stated on the front page of the paper, the manuscript was first submitted to Oncogene on June 14th 2004. At that point, the figure was already included and remained unchanged throughout the entire revision process up to final publication. The manuscript entitled u201cp14ARF induces G2 cell cycle arrest in p53- and p21-defienct cancer cells by down-regulating p34cdc2 kinase activityu201d (shown in the left panel) by G. Normand from our group was first submitted to The Journal of Biological Chemistry (JBC) at a later time point, i.e. on November 1st 2004. This is also shown on the front page of the published paper. Apparently, the Western blots shown there (Figure 6A) stem from the very same set of experiments (and their replicates). This may be seen easily by comparing the p53 bands. During assembly of Figure 6A, u00df-actin controls were obviously mixed up. The most plausible explanation is, that the blots were split u2013 a method commonly used at that time. Unfortunately, re-using some of the blots and mixing up controls was not uncovered by cross-checking the manuscripts before final submission or while editing the proofs. Partly re-using the Western blots in part in another publication was certainly not done on purpose but happened as a consequence of parallel preparation of the two papers by two separate authors. In any event, the publication of the work in Oncogene was first. JBC will be informed and the issue of how to handle partial double publication (concerning 2 other parameters) as well as splitting blots without proper mark-up will be addressed. #2 Thank you for pointing out, that the histograms shown are identical. A strongly assume that the Ad-lacZ histogram for the 10.1% value was misplaced during copy paste retrieval of the pictures from the CellQuest analysis software of the flow-cytometer. I am quite confident, that this happened by accident, but certainly not on purpose. After an intense search, a correct version of Figure 6A-D showing the correct histogram for the 10.1% value was found (shown below). Let me apologize for that mistake. Nevertheless, I would like to emphasize that in a number of other publications we were able to show that the Ad-lacZ control adenovirus does not trigger caspase activation in different cancer cell lines, as determined by the very same flow-cytometric method (Hemmati et al., Oncogene (2006) 25, 6582-6594: Figure 5 or Hemmati et al., Oncogene (2008) 27, 6707-6719: Figure 7a). P. G. (still unable to create a pubpeer account) ![file] ,