microRNA-532 suppresses the PI3K/Akt signaling pathway to inhibit colorectal cancer progression by directly targeting IGF-1R
Authors: Xiaodong Wang
Yue Zhao
Ying Song
Xiangfu Ding
Journal: American journal of cancer research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; PI3K/Akt pathway; insulin-like growth factor 1 receptor; microRNA-532.
Affiliations: Department of Digestive Endoscopy, The Second Hospital of Jilin UniversityChangchun, Jilin, P. R. China., Department of Vascular Surgery, The China-Japan Union Hospital of Jilin UniversityChangchun, Jilin, P. R. China., Department of Thyroid Surgery, The Second Hospital of Jilin UniversityChangchun, Jilin, P. R. China.

Abstract:  Substantial evidence has shown that numerous microRNAs (miRNAs) are deregulated in colorectal cancer (CRC) and that their dysregulation is involved in CRC formation and progression. miRNA-based targeted therapy that inhibits or restores expression may be a promising therapeutic approach for anti-cancer therapy. Therefore, a comprehensive investigation of the mechanisms underlying CRC occurrence and development may help identify effective therapeutic targets for the therapy of CRC, thus improving the prognosis of patients with this disease. This study showed that miRNA-532 (miR-532) was significantly down-regulated in CRC tissues and cell lines. Low miR-532 expression strongly correlated with aggressive clinicopathological characteristics, including tumor size, lymphatic metastasis and TNM stage. Exogenous expression of miR-532 restricted cell proliferation, colony formation, migration and invasion; promoted cell apoptosis in vitro; and reduced tumor growth in vivo. Mechanistically, insulin-like growth factor 1 receptor (IGF-1R) was determined to be a novel direct target gene of miR-532 in CRC. In clinical CRC tissues, the expression of miR-532 was inversely correlated with that of IGF-1R, which was clearly overexpressed in CRC tissues. Furthermore, IGF-1R silencing simulated the tumor-suppressing roles of miR-532 in CRC. Moreover, recovered IGF-1R expression antagonized the inhibitory effects of miR-532 overexpression on CRC cells. Notably, miR-532 overexpression inhibited activation of the PI3K/Akt signaling pathway in CRC, both in vitro and in vivo. These results indicate that miR-532 plays an important role in CRC development, partly by directly targeting IGF-1R and regulating the PI3K/Akt signaling pathway. Thus, the miR-532/IGF-1R axis has clinical significance in the therapy of patients with CRC. 

Retracted: Yes

PubPeer comments:
 Unexpected similarity between a panel from [Wang et al (2019)] , and one from the present paper. ![file] Figs 2D, 4D, 5D from here, for context: ![file] Figs 2D, 5D, 6E from Wang et al (2019): ![file] , 
 Figs 2D, 4D, 5D again: ![] Light brown box marks a panel that matches one from [Ren et al (2019)] . ![] ![] , 
 Clockwise from left: - Fig 7A from [Wang et al (2018)] .  The representative images of the miR-769 mimics and miR-NC [SW480] tumor xenografts. Rotated through 90 deg to facilitate comparison. - **Fig 7B from [Song et al (2018)] **.  Representative images of the miR-532 mimics and miR-NC [SW480] xenograft tumors . - Fig 7A from [Lv et al (2019)] .  The representative images of tumor xenografts obtained from [HOS] agomir-NC and agomir-761 groups . - Fig 7A from [Lyu et al (2019)] .  Representative images of the [Y79] tumor xenografts derived from miR-485 mimics or miR-NC groups . - Fig 7A from [Yao et al (2018)] .  Photographs of tumor xenografts derived from miR-641 mimics- or miR-NC-transfected HeLa cells . ![file] Certain pairs of tumors appear to be the same (colored boxes). All five institutions seem to be using the same distinctively-battered ruler. , 
 Retraction, September 2021: https: www.ncbi.nlm.nih.gov pmc articles PMC8493388 A contestant for the prize of this year s most vague retraction notice:  In this article, we recently found that the unreproducible of regulatory actions of miR-532 on the apoptosis of colorectal cancer. For the sake of scientific rigor, we think it is most appropriate to retract the manuscript. All authors agree to retract the manuscript. ,