E3 ubiquitin ligase SMURF2 prevents colorectal cancer by reducing the stability of the YY1 protein and inhibiting the SENP1/c-myc axis
Authors: Qianfu Gao
Zeyan Zhang
Shanchao Wang
Journal: Gene Therapy (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Genetic association; E3 ubiquitin ligase SMURF2; colorectal cancer (CRC); tumor-promoting gene YY1; malignant phenotypes
Affiliations: Anorectal Department, Linyi People's Hospital, Linyi, 276003, PR China., Anorectal Department, Linyi People's Hospital, Linyi, 276003, PR China. .

Abstract:  Genetic association between E3 ubiquitin ligase SMURF2 and colorectal cancer (CRC) has been identified, while the mechanism remains undefined. Tumor-promoting gene YY1 represents a downstream factor of SMURF2. The study was designed to evaluate the effect of SMURF2 on the malignant phenotypes of CRC cells and the underlying mechanism. The expression pattern of SMURF2 and YY1 in CRC clinical tissues and cells was characterized by immunohistochemistry (IHC) and Western blot. Gain- and loss-of-function experiments were conducted to assess the effect of SMURF2 and YY1 on the behaviors of CRC cells. After bioinformatics analysis, the relationship between YY1 and SENP1 as well as between SENP1 and c-myc was determined by luciferase reporter and ChIP assays. Rescue experiments were performed to show their involvement during CRC progression. Finally, in vivo models of tumor growth were established for validation. SMURF2 was lowly expressed and YY1 was highly expressed in CRC tissues and cells. YY1 overexpression resulted in promotion of CRC cell proliferation, migration, and invasion, which could be reversed by SMURF2. Furthermore, SMURF2 could induce ubiquitination-mediated degradation of YY1, which bound to the SENP1 promoter and upregulated SENP1 expression, leading to enhancement of c-myc expression. The in vivo data revealed the suppressive role of SMURF2 gain-of-function in tumor growth through downregulation of YY1, SENP1, or c-myc. Altogether, our data demonstrate the antitumor activity of SMURF2 in CRC and the anti-tumor mechanism associated with degradation of YY1 and downregulation of SENP1/c-myc. 

Retracted: No

PubPeer comments:
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 Thanks for the comments. I suppose the point is about why the GADPH bands of the two images(Fig 2, Fig 5) are consistent. In fact, the two figures are using the same baseline Marker. Under the condition of the same intervention condition, samples of each group were prepared and run on one PVDF membrane. After detecting the development of the first protein(such as NOX2), the primary and secondary antibodies on the membrane were washed off by a stripping buffer. Then the primary antibodies of another protein(such as p-PKC) were added. The primary and second antibody stripping buffer(Beyotime, P0025) which was used in our experiments, has been shown to be effective in other articles. For example, 1.u00a0Liu C, Huang J, Li H, Yang Z, Zeng Y, Liu J, Hao Y, Li R . Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-u03baB GR signaling pathways incombined radiation and burn injury in rats. SCI REP-UK . 2016 Jun 7;6:27499. (IF 4.011) 2.u00a0Zhu W, Mao Z, Zhu C, Li M, Cao C, Guan Y, Yuan J, Xie G, Guan X. Adolescent exposure to cocaine increases anxiety-like behavior and induces morphologic andneurochemical changes in the hippocampus of adult rats. Neuroscience . 2016 Jan 28;313:174-83. (IF 3.244). In conclusion, itu2019s the same PVDF membrane, so the GADPH band only expose for one time. ,