<p>microRNA-877 inhibits malignant progression of colorectal cancer by directly targeting MTDH and regulating the PTEN/Akt pathway</p>
Authors: Hui Li
Lunqiang Zhang
Haiping Pei
Lijun Cao
Chenglong Li
Haiding Zou
Hongqin Li
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: PTEN/Akt pathway; colorectal cancer; metadherin; microRNA-877.
Affiliations: Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Hunan 410008, People's Republic of China., Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Hunan 410011, People's Republic of China.

Abstract:  Background: Recently, microRNA-877-5p (miR-877) was recognized as a cancer-associated miRNA in hepatocellular and renal cell carcinomas. However, little is known regarding its expression pattern and role in colorectal cancer (CRC) tumorigenesis. Material and methods: In the present study, reverse-transcription quantitative polymerase chain reaction was performed to detect miR-877 expression in CRC tissues and cell lines. A series of functional experiments were used to determine the effects of miR-877 upregulation on CRC cell proliferation, colony formation, apoptosis, migration, and invasion. In addition, the regulatory role of miR-877 in tumor growth was examined in vivo using a xenograft experiment. More importantly, the mechanisms underlying the action of miR-877 in CRC were explored. Results: A significant decrease in the expression of miR-877 was observed in CRC tissues and cell lines. Low miR-877 expression correlated with lymph node metastasis and TNM stage of CRC patients. Functional experiments revealed that ectopic expression of miR-877 suppressed CRC cell proliferation and colony formation ability, induced cell apoptosis, inhibited cell migration and invasion in vitro, and reduced tumor growth in vivo. Metadherin (MTDH) was recognized as a direct target of miR-877 in CRC cells. It was notably overexpressed in CRC tissues, and its expression was inversely correlated with that of miR-877 expression. Furthermore, MTDH knockdown simulated the tumor suppressor activity of miR-877 in CRC cells. MTDH restoration impaired the suppressive effects of miR-877 on malignant phenotypes of CRC cells. In addition, miR-877 inhibited the activation of the PTEN/Akt signaling pathway by regulating MTDH expression both in vitro and in vivo. Conclusion: Collectively, these results demonstrate that miR-877 inhibits the progression of CRC, at least partly by the direct targeting of MTDH and regulation of the PTEN/Akt pathway. Thus, miR-877 may serve as a potential therapeutic target for the treatment of patients with CRC. 

Retracted: Yes

PubPeer comments:
 Figs 3A,B and 5E, F. ![file] Figs 2C, 5C from [Zhou et al (2019)] . ![file] Overlaps marked. Different identifications. Two separate groups of authors from unrelated institutions seem to have had access to the same pool of images, from which they were drawing images randomly to illustrate their descriptions of experiments. , 
 We really appreciate your interest to our manuscript. We will look for the original data and check it. Also, we will repetat the Transwell experiments to confirm the observations. , 
 #2 Could you check the flow-cytometry and colony-formation results as well? , 
 ![file] Figs 3A,B Ectopic miR-877 expression suppresses the migratory and invasive abilities of CRC cells. miR-877 mimics or miR-NC was introduced into SW480 and HCT116 cells. The influence of miR-877 upregulation on the migration (A) and invasion (B) abilities of SW480 and HCT116 cells was evaluated using Transwell migration and invasion assays. ![file] Figs6 E,F Migration and invasion of SW480 and HCT116 cells co-transfected with miR-877 mimics and pc-MTDH or empty pcDNA3.1 were examined through Transwell migration and invasion assays. *P 0.05 versus miR-NC. #P 0.05 versus miR-877 mimics + pcDNA3.1. Dear Dr.Elisabeth M Bik, Thanks a lot for pointing out our mistake.We are very sorry for the confusing the representative images. We will contact the editorial office to address this and prepare to repeat the experiment. Thank you again for your valuable comments. Best regards. Haiping Pei , 
 #4 1. I am not Dr Elisabeth Bik, though it is a compliment to be mistaken for her. 2. How did this paper, and Zhou et al (2019), use the same representative images?  Confusing the representative images can happen to anyone, but confusing them with an unrelated paper by different authors is something that calls out for an explanation. , 
 https: twitter.com TigerBB8 status 1406084673638486017  The duplication of our apology with someone else s paper is the fault of an outside contractor to whom we outsourced the replies . , 
 Figs 2D, 5D, 6D. ![file] One panel (bright green box) previously appeared in Figs 2G,H and 4G,H from [Ji et al (2017)] , and in Figs 2D, 5D of [Hu, XIn Wang (2018)] . ![file] Here in context: ![] ------------------------------------------------ ![] There may be other matching panels, or matches with panels elsewhere in this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 Retracted, [28 September 2021] . -------------------------- The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2D, 3B and 6E with similar images from unrelated articles, specifically: - Figure 2D, panel HCT-116 miR-877 mimics appears to have been duplicated with a similar image in Figure 2G from Ji et al, 2017 and Figure 2D from Hu et al, 2018 . - Figure 3B, panel HCT-116 miR-877 mimics appears to have been duplicated with a similar image in Figure 2C from Zhou et al, 2019 (DOI: 10.3892 etm.2019.7676). - Figure 6E, panel SW-480 miR-877 mimics+pcDNA3.1 appears to have been duplicated with a similar image in Figure 5C from Zhou et al, (DOI: 10.3892 etm.2019.7676). The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,