MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1
Authors: Bo Shi
Kexin Huang
Guoyu Fan
Lan Wu
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: microRNAs; tumor development; progression; metastasis; miR-128
Affiliations: Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., The Experiment Center, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China., Department of Oncology, The Center Hospital of Jilin City, Fengman, Jilin 132011, P.R. China.

Abstract:  Evidence has shown that microRNAs play important roles in tumor development, progression, and metastasis. miR-128 has been reported to be deregulated in different tumor types, whereas the function of miR-128 in colorectal carcinoma (CRC) largely remains to be elucidated. The aim of the present study was to investigate the clinical significance, biological effects and underlying mechanisms of miR-128 in CRC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. It was found that the expression of miR-128 was downregulated in CRC tissues and cell lines as determined by RT-qPCR. Furthermore, the expression of miR-128 in tumor tissues was significantly negatively correlated with TNM stage and lymph node metastasis in CRC patients. Functional assay revealed that the overexpression of miR-128 inhibited CRC cell proliferation, colony formation, migration and invasion and promoted apoptosis in vitro, and suppressed CRC xenograft tumor growth in vivo. In addition, insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling, was confirmed as a direct target of miR-128 by a luciferase reporter assay. Western blot analysis indicated that the overexpression of miR-128 significantly downregulated IRS1 expression and its downstream Akt signaling in CRC cells. Moreover, miR-128 was negatively associated with IRS1 in CRC tissues compared to adjacent non-tumor tissues. Taken together, these data suggested that miR-128 serves as a tumor suppressor and blocks CRC growth and metastasis by targeting IRS1. 

Retracted: Yes

PubPeer comments:
 Fig 2.  Overexpression of miR-128 inhibits CRC cells proliferation and colony formation. (A) miR-128 mimic restored miR-128 expression in SW480 cells. (B) Cell proliferation was determined by CCK8 assay in SW480 cells following transfection with miR-128 mimic or miR-NC. (C) Cell colony formation was determined in SW480 cells following transfection with miR-128 mimics or miR-NC.  Fig 2 from [Wu et al (2016)] .  MiR-144 overexpression reduces proliferation and colony formation in Hep2 cells. A. qRT-PCR determined miR-144 expression in Hep2 cells transfected with miR-144 mimic or miR-NC. B. CCK8 assay were performed to determined cell proliferation in Hep2 cells transfected with miR-144 mimic or miR-NC. C. Colony formation was determined in Hep2 cells transfected with miR-144 mimic or miR-NC .  Could the authors comment on the similarity of some of these panels? UPDATE: see also Figs 2C, 5C from [Yang et al (2018)] .  , 
 Figure 6.  miR-128 regulates AKT signaling pathway and its downstream gene. Western blotting determined AKT, p-AKT, cyclin D1, Bcl-2 and MMP-2 protein expression in SW480 cells transfected with miR-128 mimic or miR-NC. u03b2-actin was used as an internal control , with two bands flipped or rotated.  *[left]* Fig 5B from [Gong et al (2016)] .  IGF2BP1 ... protein expression in human NSCLC tissues and their corresponding normal tissues were determined by ... western blot . *[right]* Fig 6D.  Detection of IGF2BP1 protein expression in tumor tissues by Western blot , with one band flipped.  Some remarkable similarities. , 
 #2 Fig 6 again.  Fig 4D from [Dong et al (2016)] .  , 
 Dear Hoya Camphorifolia, Thank you for your comment. Our team will investigate these questions, and reply you as quickly as possible. Thank you again for your heip. Best regards , 
 In an attempt to be systematic, I drew up a chart of loading controls. I hope this helps with investigations.  They appear in ten papers (so far). I have listed them in order of PMID but I have no idea of the actual order of publication, or who could have borrowed from whom: Zhang et al (2015).  MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma . **1** pubmed: 26156803 doi: 10.1007 s13277-015-3749-8 https: pubpeer.com publications 0E1553149DB9C07C79AE9AA98B423A Wen et al (2015).  miR-126 inhibits papillary thyroid carcinoma growth by targeting LRP6 . **1, 2, 3** pubmed: 26239517 doi: 10.3892 or.2015.4165 https: pubpeer.com publications 6ABA315E06CFE3A6221A98EFABDD67 **Wu et al (2015)**.  MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1 . **4** pubmed: 26352220 doi: 10.3892 or.2015.4251 https: pubpeer.com publications A879465BECECEBC98D393381F4F78F Ren et al (2016).  MicroRNA-92a promotes growth, metastasis, and chemoresistance in non-small cell lung cancer cells by targeting PTEN . **1,2,4** pubmed: 26432332 doi: 10.1007 s13277-015-4150-3 https: pubpeer.com publications A33D1FC9CB601204841FD284BF215A Li et al (2016).  miR-29a suppresses growth and metastasis in papillary thyroid carcinoma by targeting AKT3 . **1,4,5** pubmed: 26482618 doi: 10.1007 s13277-015-4165-9 https: pubpeer.com publications 7309F9AAD9BC0C7F8543AF230CC3CC Pang et al (2015).  miR-154 targeting ZEB2 in hepatocellular carcinoma functions as a potential tumor suppressor . **1,2,3,4** pubmed: 26503460 doi: 10.3892 or.2015.4321 https: pubpeer.com publications DF107B851B56324705EA0923E5A52C Dong et al (2016).  MiR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12 . **1** pubmed: 26847706 doi: 10.3892 or.2016.4604 https: pubpeer.com publications B12851EE8DAD041AF42E8DD460F790 Han et al (2016).  MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein . **3** pubmed: 27221209 doi: 10.3892 or.2016.4810 https: pubpeer.com publications 2B28DA2CC5F850AC09F4F095B7FE6A Liu et al (2016).  miR-449a inhibits proliferation and invasion by regulating ADAM10 in hepatocellular carcinoma . **1, 4** pubmed: 27398144 https: pubpeer.com publications D623C4D95CCB4F678FCF78CACF069E Liu et al (2016).  miR-124 inhibits proliferation and invasion of human retinoblastoma cells by targeting STAT3 . **2** pubmed: 27498908 doi: 10.3892 or.2016.4999 https: pubpeer.com publications 0422141E07B8697374077B49E6E926 ----------------------------------------------- In the present case we have Fig 5D.  , 
 Just one more question. Fig 7.  miR-128 inhibits tumor growth tumorigenicity in vivo by inhibiting IRSI. (A) Images of tumors derived for different groups .  Fig 6 from [Pang et al (2015)] .  miR-154 suppresses tumor growth in a mouse xenograft model. (A) Images of the tumor tissues.  Does this seem unusual? , 
 #6 Another attempt to deconstruct this stamp collection. *[right]* Fig 7 again. *[left]* Fig 5A from [Li et al (2015)] .  Images of tumor tissue with different group collected after sacrifice at day 21 .  For comparison with *[left]* Fig 7A from [Liu et al (2014)] .  Images of tumor tissue with different plasmid treatments collected after sacrifice at day 35. *[right]* Fig 7A from [Zhang et al (2015)] .  Images of the tumor tissues from the different groups .  Surprising similarities after a 180-deg flip. , 
 Retracted [12 July 2021] . ---------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the western blotting data shown in Figs. 5D and 6 bore unexpected similarities to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,