MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer
Authors: Xiaohong Lv
Yang Li
Huan Xia
Journal: International Journal of Oncology (2016)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-107; non-small cell lung cancer; progression; metastasis; TNM stage
Affiliations: Department of Respiratory Medicine, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China.

Abstract:  Abnormal expression of microRNA-107 (miR-107) was found in non-small cell lung cancer (NSCLC). However, little is known about its role and molecular mechanism in NSCLC progression and metastasis. Therefore, the aims of this study were to clarify the potential role of miR-107 and molecular mechanism in NSCLC progression and metastasis. Quantitative real-time polymerase chain reaction assay showed that miR-107 expression levels were significantly decreased in NSCLC tissue and cell lines. Low miR-107 levels in tumor tissue correlated with advanced TNM stage and lymph node metastasis. Function assays showed that overexpression of miR-107 suppressed cell proliferation, migration and invasion in A549 cells in vitro, and inhibited NSCLC tumor growth in vivo. Further mechanism assays suggested the brain-derived neurotrophic factor (BDNF) was identified as a target gene of miR-107 in NSCLC cells. In addition, BDNF expression was upregulated, and inversely correlated with miR-107 in NSCLC tissues. Enforced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-107 on NSCLC proliferation, migration and invasion. miR-107 overexpression or downregulation of BDNF was able to inhibit activation of PI3K/AKT signaling pathway. Taken together, our findings present the first evidence that miR-107 could suppress NSCLC metastasis by targeting BDNF and indirectly regulating PI3K/AKT signaling pathway, which might lead to a potential therapeutic strategy focusing on miR-107 and BDNF for human NSCLC. 

Retracted: Yes

PubPeer comments:
 Fig 2D inset.  The mice were sacrificed at 30 days after inoculation, and the tumors were weighed . ![file] Could the authors comment on the re-appearance of two of these tumors in Fig 6B from [Li et al (2018)] ?  Tumor tissues were imaged after the mice were sacrificed . ![file] , 
 *[left]* Fig 7.  miR-107 inhibits the PI3K AKT signal pathway. PI3K, p-PI3K, AKT and p-AKT protein expression was detected in A549 cells transfected with miR-107 mimic miR-NC or si-BDNF si-NC by western blotting. u03b2-actin was used as the internal control. *[right]* Fig 6 from [Liu et al (2015)] .  PI3K AKT signaling pathway inactivation is associated with PTEN expression. PTEN protein and the downstream genes PI3K and phosp-AKT protein expression were determined in HCC cells after transfection with miR-494 mimic or anti-miR-494 . ![file] Also *[left]* Fig 5C of [Song et al (2015)] .  Western blotting of EGFR protein expression in the HeLa cells after transfection with the miR-133a mimic or miR-Ctrl. u03b2-actin was used as an internal control. *[right]* Fig 3c from [Zhang et al (2015)] .  The expression levels of MMP-2 and MMP-9 were determined by Western blot after being transfected with miR-133a or miR-NC. GAPDH was used as internal control . ![] Those threads link to further appearances of the bands. , 
 #1 Fig 2D inset again, now with more colored boxes... ![] ... for ease of comparison with Fig 6B of [Yu et al (2016)] . ![] , 
 Retracted [13 July 2021] . ------------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that the western blotting data featured in Fig. 7, and the tumour images in Fig. 2, were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. 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 *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 satisfactory response. The Editor apologizes to the readership for any inconvenience caused. ,