miR‑802 inhibits the aggressive behaviors of non‑small cell lung cancer cells by directly targeting FGFR1
Authors: Yinyin Qin
Xiaoxiang Li
Jun Li
Jiexia Zhang
Chengzhi Zhou
Shiyue Li
Journal: International Journal of Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: miR-802; NSCLC; FGFR1; PI3K/Akt/mTOR pathway; tumor suppressor
Affiliations: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, Department of Respiration, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China., Department of Neurosurgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, P.R. China.

Abstract:  Emerging reports have revealed that several microRNAs (miRNAs) are abnormally expressed in non‑small cell lung cancer (NSCLC). miRNAs have been identified as oncogenes or tumor suppressors, and regulate various biological processes including oncogenesis and development. miR‑802 is dysregulated in multiple types of human cancer, and exerts tumor‑suppressive or promoting roles. However, the expression levels and functional roles of miR‑802 in NSCLC remain largely unknown. In the present study, miR‑802 expression was demonstrated to be decreased in NSCLC tissues and cell lines. A low miR‑802 expression was significantly correlated with the tumor stage, lymph node metastasis and brain metastasis in NSCLC patients. Restoring miR‑802 expression inhibited NSCLC cell proliferation and colony formation, induced cell apoptosis, decreased cell migration and invasion in vitro, and hindered in vivo tumor growth. Mechanistically, fibroblast growth factor receptor 1 (FGFR1) was confirmed as the target gene of miR‑802 in NSCLC cells. In addition, FGFR1 silencing mimicked the tumor‑suppressing roles of miR‑802 upregulation in NSCLC cells. Furthermore, rescue experiments revealed that FGFR1 reintroduction rescued the miR‑802‑induced inhibition of the malignant phenotypes in NSCLC cells. Notably, miR‑802 was able to deactivate the phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway in NSCLC cells in vitro and in vivo. Overall, these results demonstrated that miR‑802 could downregulate FGFR1 expression, thereby deactivating the PI3K/Akt/mTOR pathway and inhibiting the malignant development of NSCLC. Thus, miR‑802 may be a therapeutic candidate for patients with NSCLC. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 4D, 5D.  The apoptosis rate of H522 and H460 cells transfected with miR-802 mimics or miR-NC was assessed via Annexin V and PI staining ;  Annexin V and PI staining was used to detect the apoptosis rate of H522 and H460 cells following FGFR1 silencing ;  apoptosis ... of the aforementioned cells were assayed . ![file] Panel marked with lavender rectangle also appears in Figs 2D, 6D of [Li You (2018)] .  The apoptosis rate in Y79 and WERI-RB1 cells transfected with miR-758 mimics or miR-NC was evaluated using a flow cytometric assay ;  Cell ... apoptosis in the aforementioned cells were evaluated using... flow cytometric assays . ![file] ![file] , 
 Figs 2D, 4D, 5D again: ![] The panel marked with a blue box reappears in Figs 2C, 5C, 6C of [Jiao et al (2019)] . ![] ---------------------------------------------- The panel marked with a purple box reappears in Figs 2D, 5D, 6D of [Kang et al (2019)] . ![] ![] , 
 *[left]* **Fig 7A from [Zhang et al (2019)] **.  Photograph of tumor xenografts obtained from nude mouse injected with miR-802 mimics- or miR-NC-transfected H460 cells . Rotated through 90 deg to facilitate comparison. *[upper right]* Fig 8A from [Wang, Xiao Zhao (2019)] .  miR-675 mimics or miR-NC were transfected into TPC-1 cells and then injected to nude mice. A representative image of tumor xenografts is shown . *[lower right]* Fig 7B from [Tan et al (2019)] .  Representative images of tumor xeno-grafts derived from H460 cells transfected with agomir-625 or agomir-NC . ![file] Two pairs of tumors appear to be the same, seen at slightly different angles (red rectangles). Note also that all three institutions seem to be using a single ruler, with a distinctive stain at the lower right. , 
 Retracted [4 July 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the data panels showing results from flow cytometric experiments in Figs. 2D, 4D and 5D, and tumor images shown in Fig. 7A, were strikingly similar to data that had appeared 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 *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. ,