miR-126 inhibits papillary thyroid carcinoma growth by targeting LRP6
Authors: Lin Bai
Tongtong Wang
Qingjie Ma
Jie Zhao
Haishan Zhang
Qiang Wen
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-126; tumor suppressor; papillary thyroid carcinoma; tumorigenicity; lymph node metastasis
Affiliations: Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China., Department of Surgery, China-Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 13033, P.R. China.

Abstract:  microRNA-126 (miR-126) has been reported to play tumor suppressor roles in various types of cancers. Although it has been reported that miR-126 expression is downregulated in papillary thyroid carcinoma (PTC), the precise role and underlying molecular mechanism of miR-126 in PTC remains unclear. Therefore, the aims of the present study were to investigate the role and potential mechanism of miR-126 in tumorigenicity of PTC in vivo and in vitro. We observed that the miR-126 expression level was significantly downregulated in PTC tissue and PTC cell lines, the aberrant expression of miR-126 was correlated with lymph node metastasis, tumor size and TNM stage. We also showed that restoration of miR-126 in PTC cells inhibited cell proliferation, colony formations, migration and invasion, promoted cell apoptosis and cell cycle arrest at G1 stage in vitro, as well as inhibited tumor growth and decreased tumor volume and weight in vivo. Furthermore, low-density lipoprotein receptor‑related protein 6 (LRP6), a regulator of the Wnt/β‑catenin signaling cascade, was identified as a crucial target gene of miR-126. Overexpression of miR-126 inhibited LP6 expression on mRNA and protein levels, and deactivate Wnt/β-catenin signaling pathway. These results suggested that miR-126 functions as a tumor-suppressive miRNA by targeting LRP6 regulating Wnt/β-catenin signaling pathway and represents a therapeutic target for PTC. 

Retracted: Yes

PubPeer comments:
 Fig 5B.  Western blotting determined cyclin D1, MMP-7, CCND1 and c-Myc expression in TPC-1 cells after transfected with miR-126 mimic or miR-Ctrl. u03b2-actin was the internal control. ![file] See also Fig 6A from [Liu et al (2016)] .  After 72 h of transfection, PAX6 protein levels in indicated cells were detected by western blot analysis . ![file] Fig 6B from [Ren et al (2016)] .  PTEN expression on ... protein level (b) was determined in A549 cells transfected si-PTEN or si-NC. GAPDH was used as an internal control . ![file] Could the authors comment on the appearance of the same loading control? The loading control is not the only similarity between *[left]* 6B from Ren et al and *[right]* the present 6B. ![file] , 
 *[below]* Fig 4C.  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. *[above]* Fig 5B from [Dong et al (2016)] .  Western blot analysis of CXCL12 protein expression in primary PTC tissues (T) and the matched adjacent normal tissues (ANT) from the same patient. The loading control (actin or GAPDH) appears to be the same. Substantive bands involve the same lanes, though rearranged and flipped horizontally. ![file] , 
 *[below]* Fig 4C again.  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. *[above]* Fig 8F from [Li et al (2016)] .  AKT3 expression on ... protein level (f) in tumor tissue were determined. GAPDH was used to an internal control. Unexpected similarities. ![file] , 
 *[right]* Fig 6D.  Determination of LRP6 protein expression level of tumor tissue by western blotting. u03b2-actin was used as an internal control. *[left]* Fig 5D from [Han et al (2016)] .  Western blot analysis of the relative expression of XIAP in four CRC cell lines compared with the normal colonic cell line (NCM460). ![file] I have a concern. , 
 In an attempt to be systematic, I drew up a chart of loading controls. ![file] 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 Figs 4C, 5B, 6D. ![file] ![file] ![file] , 
 Retracted [31 May 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. 4C, 5B and 6D 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 were already under consideration for publication, or 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. ----------------------------------------- Background [here] . ,