Downregulation of microRNA‑629‑5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low‑density lipoprotein receptor‑related protein 6
Authors: Guoqiang Yan
Lei Wang
Chenyao Li
Yuhang Zhao
Meng Yue
Journal: International Journal of Molecular Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: miR-629; colorectal cancer; tumor progression; proliferation; apoptosis
Affiliations: Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China

Abstract:  Aberrant expression of numerous microRNAs (miRNAs/miRs) in colorectal cancer (CRC) significantly affects disease progression. Recently, miR‑629‑5p (miR‑629) was identified as a tumor‑promoting miRNA in the malignant processes of a number of human cancers. However, few studies have been conducted regarding expression profiles and detailed roles of miR‑629 in CRC. In the present study, reverse transcription‑quantitative polymerase chain reaction was used to assess miR‑629 expression in CRC tissues and cell lines. Cell Counting Kit‑8 assay, flow cytometry and Transwell assays were performed to determine the in vitro effects of miR‑629 on CRC cell proliferation, apoptosis, and metastasis, respectively. Xenograft models were employed to determine the in vivo effects of miR‑629 on tumor growth in nude mice. Molecular mechanisms underlying the activity of miR‑629 in CRC cells were explored. miR‑629 expression decreased in CRC tissues and cell lines. The decreased aberrant miR‑629 expression was significantly associated with tumor size, lymphatic metastasis and tumor‑node‑metastasis stage of CRC, and was a predictor of poor prognosis. Restoring miR‑629 expression attenuated CRC cell proliferation, migration and invasion; promoted cell apoptosis in vitro; and inhibited tumor growth in vivo. Low‑density lipoprotein receptor‑related protein 6 (LRP6) was a direct target gene of miR‑629 in CRC cells. Furthermore, the effect of LRP6 knockdown was similar to that of miR‑629 overexpression in CRC cells. Restoration of LRP6 expression neutralized the effects of miR‑629 in CRC cells. miR‑629 suppressed the activation of the Wnt/β‑catenin pathway through LRP6 regulation both in vitro and in vivo. In conclusion, miR‑629 suppressed the development and progression of CRC by directly targeting LRP6 and inhibiting the Wnt/β‑catenin pathway both in vitro and in vivo. Therefore, miR‑629 may be a novel prognostic biomarker and therapeutic target in CRC. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5E.  apoptosis of HCT116 and SW620 cells upon miR-629 overexpression ;  apoptosis... of HCT116 and SW620 cells transfected with LRP6 siRNA or NC siRNA ;  apoptosis of HCT116 and SW620 cells treated as above . ![file] Orange box marks a panel that also features in Figs 2C, 5C, 6C of [Cheng et al (2020)] . ![file] ![file] , 
 *[right]* Fig 7B.  The representative images of the [HCT116] tumor xenografts obtained from the agomir-629 group and the agomir-NC group. *[left]* Fig 9A from [Pang et al (2019)] .  A representative image of the [BGC-823] tumor xenografts obtained from the agomir-628 and agomir-NC groups. ![file] Different cell-lines, different treatments, different authors, same tumors (slightly rotated). , 
 Clockwise from upper left: - Fig 9A from [Pang et al (2019)] .  A representative image of the [BGC-823] tumor xenografts obtained from the agomir-628 and agomir-NC groups. Rotated through 90 deg to facilitate comparison. - **Fig 7B again**.  The representative images of the [HCT116] tumor xenografts obtained from the agomir-629 group and the agomir-NC group. - Fig 7A from [Yang et al (2019)] .  Representative images of the tumor xenografts 4 weeks after inoculation with U251 cells expressing miR-559 mimics or miR-NC. Rotated through 90 deg. - Fig 8A from [Li, Li Sun (2019)] .  Photographs of tumor xenografts derived from agomir-876u2013 and agomir-NCu2013 transfected MCF-7 cells . ![file] Some pairs of tumors are more similar than one would expect, as if they are the same tumors with slightly different lighting. All four institutions seem to be using **the same ruler**, distinguished by a scrape just to the left of the 1 . Do they pass it around, like the single eye and the single tooth of the Graeae? UPDATE: Another sighting of the ruler! Fig 7A from [Li et al (2019)] ,  Representative images of tumor xenografts derived from HOS cells transfected with the miR-618 mimics or miR-NC . Rotated through 90 deg. ![] , 
 Dear Hoya Camphorifolia Thank you for your comments. Our team is checking the original data and pictures. If there is any problem, we will repeat these experiments and contact the journal for erratum. We do appreciate your careful review, and we will give further response after we checking the data. , 
 Figs 2C, 4C, 5E again. Now with a maroon box, for a panel that (mostly) matches one from Figs 2B, 4D of [Liu et al (2019)] . ![] ![] In context: ![] ------------------------- Update: A panel of Fig 2C matches a panel of Figs 1f, 2f of [Gao et al (2020)] . I have tweaked the aspect ratio for ease of comparison. ![] ![] ![] , 
 Retracted [29 October 2021] . ---------------------------- Following the publication of the above paper, it was drawn to the Editors attention by a concerned reader that certain of the flow cytometric data featured in Fig. 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to *International Journal of Molecular Medicine*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,