MiR-137 suppresses tumor growth and metastasis in clear cell renal cell carcinoma
Authors: Hui Gao
Haijun Qu
Kaili Liu
Zhiwu Han
Jing Li
Meizhi Wang
Journal: Pharmacological Reports (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: RLIP76; ccRCC; miR-137.

Abstract:  Background: The most frequent type of renal cell carcinoma is called clear-cell renal cell carcinoma (ccRCC) which is associated with a poor prognosis. It has been observed that miR-137 is aberrantly expressed in many different kinds of human malignancies including ccRCC. This research aims to examine the role of miR-137 in ccRCC. Methods: Quantitative RT-PCR (qRT-PCR) was applied to measure miR-137 expression in ccRCC and adjacent noncancerous tissue. Gene expression was determined by western blot. Cell Counting Kit-8 (CCK-8) assay, flow cytometry and Transwell assay were used to determine the effects of miR-137 on cell growth, apoptosis and invasion, respectively. Moreover, xenograft and pulmonary metastasis animal models were established to investigate the role of miR-137 in vivo. Results: Our findings show that there was significant downregulation of miR-137 in ccRCC tissue relative to corresponding non-cancerous tissue. Ectopic miR-137 expression in ccRCC cells led to suppression of cell growth and invasion, as well as apoptosis induction. In contrast, knockdown of miR-137 enhances proliferation and invasion, inhibits apoptosis. It also confirms that miR-137 plays a tumor supressor role in vivo. Mechanically, miR-137 directly targets the 3'-UTR of RLIP76 which is an established oncogene in ccRCC. Conclusion: MiR-137 serves as a tumor suppressor, which can be considered a potential therapeutic target in ccRCC. 

Retracted: Yes

PubPeer comments:
 At right, 5D:  RLIP76 is a direct target of miR-137 in ccRCC cells. ... D). MiR-137 expression in ccRCC tissue has a negative association with protein expression of RLIP76 in CRC specimen. At left, Fig 8D from [Gao et al (2016)] :  8. PTTG enhances metastatic potential of MCF-7 cells through FAK Akt mTOR pathway. ... D. Inhibitors of FAK Akt mTOR signaling pathway significantly abolished the changes in transcriptional repressors expressions induced by PTTG  Possible re-use of a loading control. , 
 Fig 4B (at right).  .MiR-137 exerts anti-tumor effect in vivo. A). ... B). Inhibition of miR-137 on tumor growth correlates with lower expression of RLIP76 and higher expression of cleaved caspase-3. Panels also appear in 8E of [Wang et al (2019)] (at left), picking one example out of many.  , 
 Fig 4C (below). Same images in (above), Fig 5D from [Fang et al (2019)] :  AIF suppresses tumor growth and metastasis in vivo. PTC bearing mice were divided into three group (N = 6), then treated with vehicle or, AIF (40 and 80 mg kg, every day, ip) for 30 day, respectively. ... (D) A pulmonary metastasis model was employed to validate the antimetastatic effect of AIF in vivo  , 
 #2 At right: Fig 4B again,  MiR-137 exerts anti-tumor effect in vivo. A). ... B). Inhibition of miR-137 on [renal] tumor growth correlates with lower expression of RLIP76 and higher expression of cleaved caspase-3. Left: Fig 7D from [Liu et al (2017)] ,  AF suppresses ovarian tumor growth in vivo. .... D. TUNEL, HE and immunohiostochemical assay showed AF induced apoptosis and downregulated Skp2 in vivo.  Could the authors clarify whether these images came from ovarian or renal tumors? And which markers they show? And which treatments applied? And who wrote these papers? , 
 Bottom: Figs 2E ( MiR-137 restrains cell invasion ) and 3E ( Anti-miR-137 stimulates cell invasion ). Above: Fig. 6F from [Pan et al (2018)] :  Physcion induces autophagy in the HCC cells by inactivating the JAK2 STAT3 pathway. ... (F) Cell migration and invasion abilities assayed by wound healing and Transwell invasion protocols. Middle: Fig 2B from [Gao et al (2017)] :  Effects of hispidulin on cell metastatic ability. ... B: Transwell invasion assay analyzed cell invasion in Caki-2 and A498 cells after treatment with hispidulin (10 u00b5M or 20 u00b5M).  Duplicate or triplicate panels marked. , 
 Retracted [6 November 2020] . --------------------------------------------------------------------- The Editor in Chief retracted this article [1] because of significant concerns regarding a number of Figures presented in this work, which question the integrity of the data. After publication, overlap was detected with figures in articles submitted and published within a close time frame. Figure 2E appears to contain the same images that have been published elsewhere with different labels: Figure 6F in (2, now retracted) and Figure 2B in (3). Figure 3E appears to contain the same images that have been published elsewhere with different labels: Figure 6F in (2, now retracted) and Figure 2B in (3). Figure 4B appears to contain the same images that have been published elsewhere with different labels: Figure 7D (4) and Figure 8E (5). Figure 4C appears to contain the same images that have been published elsewhere with different labels: Figure 5D (6, now retracted). Figure 5D appears to contain the same images that have been published elsewhere with different labels: Figure 8D (7, now retracted). The authors were unable to provide raw data and stated that some of the data presented were not generated as part of this study. The Editor-in-Chief therefore no longer has confidence in the integrity of the data in this article. Author Zhiwu Han agrees to this retraction. The editor and publisher were unable to contact the remaining authors Meizhi Wanga, Hui Gaob, Haijun Quc, Jing Lic, Kaili Liub about this retraction. References - Wang M, Gao H, Qu H, et al. MiR-137 suppresses tumor growth and metastasis in clear cell renal cell carcinoma. Pharmacol Rep. 2018;70:963u201371. https: doi.org 10.1016 j.pharep.2018.04.006 - Pan X, et al. Protective autophagy induced by physcion suppresses hepatocellular carcinoma cell metastasis by inactivating the JAK2 STAT3 Axis. Life Sci. 2018;214:124u201335. https: doi.org 10.1016 j.lfs.2018.10.064 - Gao MQ, et al. Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat. Am J Cancer Res. 2017;7(7):1501u201314. - Liu H, et al. Amentoflavone suppresses tumor growth in ovarian cancer by modulating Skp2. Life Sci. 2017;189:96u2013105. https: doi.org 10.1016 j.lfs.2017.09.026 - Wang L, Wang J, Zhao H, et al. Soyasapogenol B exhibits anti-growth and anti-metastatic activities in clear cell renal cell carcinoma. Naunyn-Schmiedebergu2019s Arch Pharmacol. 2019;392:551u201363. https: doi.org 10.1007 s00210-018-01607-w , 
 http: www.most.gov.cn zxgz kycxjs kycxgzdt 202201 t20220127_179206.html Google Translated Date: January 27, 2022 14:44 Source: Ministry of Science and Technology u300014. The paper  MiR-137 suppresses tumor growth and metastasis in clear cell renal cell carcinoma by Han Zhiwu of Qingdao University Affiliated Hospital as the corresponding author and Wang Meizhi as the first author. After investigation, the paper was found to be fraudulent and improperly signed. Han Zhiwu (merged with the other two papers) will be dealt with as follows: demerit for 1 year, cancellation of application or application for science and technology projects (special projects, funds, etc.), science and technology awards, and qualifications for science and technology talent titles for 7 years, cancel as a nominee or recommender , Nominated or recommenders, evaluation experts and other qualifications for 7 years, recorded in the file of scientific research integrity and dishonesty, given a scientific research integrity admonishment talk, canceled from participating in this year s evaluation, and the annual evaluation shall not be determined to be qualified or above; Processing: Demerit punishment for 1 year, cancellation of application or application for science and technology projects (special projects, funds, etc.), science and technology awards, qualifications for science and technology talent titles for 5 years, cancellation of qualifications as nominees or recommenders, nominees or recommenders, evaluation experts, etc. for 5 years , recorded in the archives of scientific research integrity and dishonesty, given scientific research integrity admonitions and talks, canceled the participation in this year s evaluation, and the annual evaluation shall not be determined to be qualified or above. u3000u3000(Notification link: https: kjc.qdu.edu.cn info 1023 3178.htm) ,