miR-125a restrains cell migration and invasion by targeting STAT3 in gastric cancer cells
Authors: Kai Guo
Shuai Qi
Zhihong Zhang
Shuguang Zhang
Liu Yang
Jie Yao
Hu Huang
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: HAS1; STAT3; gastric cancer; miR-125a.
Affiliations: Department of Cancer Biotherapy Center, Hubei Cancer Hospital, Wuhan, Hubei 430079, China., Department of Clinical Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China., Department of Gastroenterology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China., Department of Oncology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China., Department of Pharmacy, The 161th Hospital of PLA, Wuhan, Hubei 430010, China., Department of Urological Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China, ., Department of Oncology, Gong'an County People's Hospital, Jingzhou, Hubei 434000, China, .

Abstract:  Background: Recently, many microRNAs have been found to be involved in the cancer progression including miR-125a. However, the underlying mechanisms of miR-125a in gastric cancer (GC) remain to be completely elucidated. Objective: The study was to investigate the functional role of miR-125a and the expression relevance of signal transducer and activator of transcription 3 (STAT3) and hyaluronan synthase 1 (HAS1). Method: CCK-8 assay, scratch wound healing and transwell assay were conducted to identify the functional role of miR-125a in GC. In addition, using bioinformatics analysis, the target regulation relationship was found in STAT3 and miR-125a. To confirm the relationship, luciferase reporter assay was performed. More importantly, quantitative polymerase chain reaction and western blot assay were carried out to determine the association among miR-125a, STAT3 and HAS1 in GC cells. Results: Overexpressed miR-125a inhibited the migration and invasion of GC cells through scratch wound healing and transwell assay, and its knockdown displayed adverse effects, but the viability of GC cells did not show significant difference using CCK-8 assay. In addition, we identified that the knockdown of STAT3 or HAS1 remarkably suppressed the migration and invasion abilities of GC cells. Using bioinformatics analysis, miRTar, in particular, indicated that the 3'-untranslated region of STAT3 binds to miR-125a with a high score. Subsequently, we also verified that STAT3 was a target of miR-125a via luciferase reporter assay. Furthermore, we found that upregulated miR-125a expression could conspicuously constrain STAT3 expression at both protein and mRNA levels in MKN45 and NCI-N87 cells using quantitative polymerase chain reaction and Western blot assay, but no significant difference had been found in SGC 7901 cells. To further identify the regulatory relationship between miR-125a and STAT3, downregulation of miR-125a in MKN45 and NCI-N87 cells was carried out, which showed that the protein and mRNA expression levels of STAT3 were declined in two cell lines. Finally, we observed that upregulated miR-125a could lead to the decrease of HAS1 at protein and mRNA levels, whereas its knockdown revealed opposite effects. Meanwhile, we noticed that overexpression of STAT3 could induce the escalation of HAS1 at protein and mRNA expression levels and its knockdown exhibited the adverse outcomes. Conclusion: These findings indicated that miR-125a may control the HAS1 expression in GC progression by targeting STAT3, which is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in GC. 

Retracted: Yes

PubPeer comments:
 The images in Figure 2 are problematic on a number of levels. There is duplication of images (in red), the lines supposedly denoting the edges of the scratch have been added in seemingly at random in places (yellow), and not only are the images at varying degrees of magnification, some have been stretched to comical levels (green).  , 
 Thank you very much for your comments. Our research group takes this very seriously and read the paper today. We felt shocked and unnerved since we know that our data are authentic and reliable. There mightu00a0be au00a0glitch when uploading the image or whatnot.u00a0Dueu00a0to theu00a0unexpected situation, it takes time to figure out what went wrong.u00a0The crux of the matter is that our school attaches great importance to the integrity in scientific research. The mistake is absurd and ridiculous, whereas our groupu00a0didnu2019t notice this issue earlier. More oversight of our work is needed. Any personnel accountable for this mistakeu00a0will be severely dealtu00a0withu00a0withoutu00a0exception.u00a0More importantly,u00a0we will contact the editors immediately and make a correction in the firstu00a0place. Thank you again. , 
 Retracted [14 July 2020] . ------------------------------------------- At the request of the authors, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. We were notified of potential image duplication in the published article. The issues relate to images shown in Figure 2B and 2C: - Figure 2B 0 hour Panel MKN45 NC inhibitor appears to be duplicated with Figure 2B 0 hour Panel MKN45 miR-125a inhibitor. - Figure 2C Panel MKN45 Blank control appears to be duplicated with Figure 2C Panel SGC7901 Blank control, which has been magnified. - Figure 2C Panel MKN45 miR-125a mimic appears to be duplicated with Figure 2C Panel SGC7901 miR-125a mimic. - Figure 2C Panel MKN45 NC inhibitor appears to be duplicated with Figure 2C Panel NCI-N87 NC inhibitor. - Figure 2C Panel MKN45 si-STAT3 appears to be duplicated with Figure 2C Panel MKN45 si-HAS1. The authors responded promptly to our queries but reported that some of the raw data for this study was missing and could only provide some of the required raw data. The editor determined that the findings of the study were no longer supported and the authors requested for the article to be retracted. The authors wish to apologise for this error and may seek a separate publication of an updated manuscript in the future. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. , 
 Hereu2019s what our favorite tool did with this. ***     , 
 #3 Thank you for your comments. We are sorry for such errors in the figures in our manuscript. We had figured this out and explained to OncoTargets and Therapy. Back when we submitted the manuscript, there was the temporarily personnel transfer in our research group. A new personnel was brought in charge of the resubmission. He wrongly uploaded the figures for practice, which were not correspondent to our experimental results. Due to his unfamiliarity to submission process, he did not even check the figures before uploading files. That was a silly figure-wised mistake due to our oversight without checking mindfully. Later, we wanted to submit our correct figures and complete raw data, but we could not find them at that moment due to the previously improper file preservation, thus leading to the withdrawal of our manuscript. Subsequently, we repeated the experiment at once, which is almost complete now. And the results obtained are consistent with those in the manuscript, thus proving the repeatability, reliability and authenticity of our data. If you need the correct figures, we would submit them as soon as the experiment is over. If you have any further question, please contact us without condition. Thank you again. , 
 #5 A truly distressing situation for you and your team. You may wish to see other papers perhaps affected in a similar way: https: pubpeer.com search?q=authors%3A%22Zhihong+Zhang%22 (this is an author name search so perhaps some are by different authors with the same name). ,