MicroRNA‑766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway
Authors: Jianjie Zhao
Shuai Hao
Lingji Guo
Bo Gao
Zhirong Li
Wuguo Tian
Shu Zhang
Yan Jiang
Xiaohua Zhang
Yi Chen
Journal: International Journal of Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-766; papillary thyroid cancer; progression; insulin receptor substrate 2; PI3K/Akt pathway.
Affiliations: Department of Breast and Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China

Abstract:  MicroRNAs (miRNAs/miRs) are widely dysregulated in papillary thyroid cancer (PTC). Dysregulated miRNAs, together with their target genes, comprise a complex network that has been implicated in the regulation of PTC pathogenesis. Further knowledge of the functional roles of aberrantly expressed miRNAs in PTC, and the underlying molecular mechanisms, may assist in the identification of novel therapeutic targets. miR‑766 has been well studied in human cancer; however, the expression status, specific roles and regulatory mechanisms of miR‑766 in PTC remain unclear. The present study aimed to detect miR‑766 expression in PTC tissues and cell lines, to explore the biological roles of miR‑766 in the malignant biological behaviors of PTC cells, and to determine the underlying mechanism of action of miR‑766 in PTC cells. The results revealed that miR‑766 was downregulated in PTC tissues and cell lines, and its downregulation was strongly associated with TNM stage and lymph node metastasis. Overexpression of miR‑766 inhibited PTC cell proliferation, colony formation, migration and invasion, promoted cell apoptosis and reduced tumor growth in vivo. Mechanistically, insulin receptor substrate 2 (IRS2) was identified as a direct target of miR‑766 in PTC cells. IRS2 was upregulated in PTC tissues, and this was inversely correlated with miR‑766 expression. Inhibition of IRS2 simulated the tumor suppressor activity of miR‑766 in PTC cells. Restoration of IRS2 expression negated the tumor‑suppressing effects of miR‑766 overexpression on PTC cells. Notably, miR‑766 directly targeted IRS2 to inhibit activation of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway in PTC cells in vitro and in vivo. Overall, these findings indicated that miR‑766 may inhibit the malignant biological behaviors of PTC cells by directly targeting IRS2 and regulating the PI3K/Akt pathway, thus suggesting that this miRNA may be a promising therapeutic target for PTC. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 4D, 5D.  Apoptotic rate of HTH83 and TPC-1 cells transfected with miR-766 mimics or miR-NC, as detected by flow cytometry ;  Flow cytometric analysis of the apoptotic rate in the cells ;  Percentage of apoptotic cells was determined using flow cytometry. ![file] Light green box: compare with matching panels in Figs 3B, 5D of [Shen et al (2018)] , ![] and Figs 2D, 5D, 6D of [Li et al (2018)] . ![] ---------------------------------------------------- Blue-grey box: see matching panel in Figs 2D, 5D, 6D of [Wu et al (2018)] . ![file] ------------------------------------ Bright green box: see matching panel in Figs 2D, 5D, 6D of [Kang et al (2017)] . ![file] A panel in Figs 2D, 5D, 6D of [Zhao et al (2017)] is not identical, but has so many points in common that it came from the same data file, plotted with different filters. ![file] ![file] , 
 #1 Figs 2D, 4D, 5D again. Now with peach box... ![file] ...with matching rectangle in Figs 3B, 5D of [Shen et al (2017)] . ![file] UPDATE: The marked panel also features in [Mao et al (2017)] . ![] ![] ------------------------------------------------ UPDATE #2. I ran out of colors to mark panels, so I will just point out another match between one panel of this paper and another of [Zhang et al (2018)] . ![file] , 
 Figs 2D, 4D, 5D again. ![] A panel matches one from [Chen et al (2019)] . ![] ----------------------------------------------------------- Here in context. ![] , 
 *[right]* Fig 7A.  Images of [TPC-1] tumor xenografts from the miR-766 mimics and miR-NC groups at 30 days . *[left]* Fig 7A from [Zhao, Li Yu (2019)] .  The images of [HOS] tumor xenografts obtained from miR-939 and miR-NC groups . ![file] Two tumors seem to have been used in both photoshoots. , 
 *[left]* Fig 2C from  MicroRNAu2011509 targets PAX6 to inhibit cell proliferation and invasion in papillary thyroid carcinoma ([Zhang et al 2018] ). *[right]* Fig 4E F. Two panels overlap after a 90-deg flip. ![file] , 
 Retracted [30 May 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2D, 4D and 5D, and certain of the tumor images featured in Fig. 7A, were strikingly similar to data appearing in different form in other articles by different authors. Furthermore, overlapping data panels were identified within this paper comparing the cell migration assay images between Figs. 2C and 4F. 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 International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. ,