MiR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12
Authors: Su Dong
Meishan Jin
Peiyou Ren
Ye Li
Jia Liu
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-137; papillary thyroid carcinoma; tumor suppressor; tumorigenesis; TNM stage
Affiliations: Department of Anesthesia, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R.¬†China., Department of Pathology, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R.¬†China., Department of Radiology, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R.¬†China., Department of Thyroid Surgery, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R.¬†China.

Abstract:  Accumulating evidence has shown that aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-137 (miR-137) has been reported as a tumor suppressor in various types of cancer. However, the biological function and underlying molecular mechanism of miR-137 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, the present study aimed to investigate the expression pattern of miR-137 and its functional significance in PTC. Quantitative RT-PCR (qRT-PCR) assay showed that miR-137 expression was significantly downregulated in human PTC tissues, and its expression was significantly negatively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that forced expression of miR-137 in PTC cells significantly inhibited proliferation, colony formation, migration and invasion in vitro. Importantly, on the basis of bioinformatic analysis and luciferase reporter assay, we found that miR-137 directly targeted the 3'-untranslated region (3'-UTR) of C-X-C motif chemokine 12 (also known as SDF-1) (CXCL12). qRT-PCR and western blot analysis further verified the results and demonstrated that miR-137 could downregulate CXCL12 expression in PTC cells. We also confirmed that CXCL12 expression was increased in PTC tissues and was inversely correlated with miR-137. In addition, our results also showed that downregulation of CXCL12 mimicked the effects of miR-137 overexpression, and upregulation of CXCL12 partially reversed the inhibitory effects of miR-137 in PTC cells. These results showed that miR-137 may function as a tumor suppressor in PTC by targeting CXCL12, suggesting that miR-137 may act as a potential target for PTC treatment. 

Retracted: Yes

PubPeer comments:
 *[above]* Fig 5B.  Western blot analysis of CXCL12 protein expression in primary PTC tissues (T) and the matched adjacent normal tissues (ANT) from the same patient. *[below]* Fig 4C from [Wen et al (2015)] .  Western blotting was used to detect LP6 protein expression in TPC-1 cells after transfected with miR-126 mimic or miR-Ctrl. u03b2-actin was the internal control. The loading control (actin or GAPDH) appears to be the same. Substantive bands involve the same lanes, though rearranged and flipped horizontally.  , 
 Fig 4D.  Western blot analysis of CXCL12 expression in K1 cells transfected with miR-137 or miR-NC. GAPDH served as the loading control .  CXCL12, or Bcl-2? Fig 6 from [Wu et al (2015)] .  , 
 Dear editor: Thank you for your conerning our paper. We would check orignial images about this paper, and reply you and Journal soon. 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 5B.  , 
 Fig 4D again, below. Above, Fig 5D of [Liu et al (2016)] .  The ADAM10 protein expression was measured in four HCC cell lines (SMMC-7721, Hep3B, HepG2, Huh-7) and normal hepatic cell line HL-7702 by western blot .  , 
 Retracted [26 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. 4D and 5B were strikingly similar 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 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. ,