MicroRNA-7 Compromises p53 Protein-dependent Apoptosis by Controlling the Expression of the Chromatin Remodeling Factor SMARCD1
Authors: Shu-Yu Lin
Chun-Fu Hong
Yu-Ting Chou
Cheng-Wen Wu
Journal: Journal of Biological Chemistry (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SMARCD1; drug resistance; epidermal growth factor receptor (EGFR); lung cancer; microRNA (miRNA)
Affiliations: From the Department of Long Term Care, National Quemoy University, Kinmen County 89250., the National Research Program for Genomic Medicine Core Facilities for Proteomics and Glycomics, Institute of Biological Chemistry, Academia Sinica, Taipei 11529., the Institute of Biotechnology, National Tsing Hua University, HsinChu 30013,. Electronic address: ., the Institute of Clinical Medicine,; Institute of Biochemistry and Molecular Biology, and; Institute of Microbiology and Immunology, National Yang Ming University, Taipei 11221, and; the Institute of Biomedical Science, Academia Sinica, Taipei 11221, Taiwan. Electronic address: .

Abstract:  We previously demonstrated that the epidermal growth factor receptor (EGFR) up-regulated miR-7 to promote tumor growth during lung cancer oncogenesis. Several lines of evidence have suggested that alterations in chromatin remodeling components contribute to cancer initiation and progression. In this study, we identified SMARCD1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 1) as a novel target gene of miR-7. miR-7 expression reduced SMARCD1 protein expression in lung cancer cell lines. We used luciferase reporters carrying wild type or mutated 3'UTR of SMARCD1 and found that miR-7 blocked SMARCD1 expression by binding to two seed regions in the 3'UTR of SMARCD1 and down-regulated SMARCD1 mRNA expression. Additionally, upon chemotherapy drug treatment, miR-7 down-regulated p53-dependent apoptosis-related gene BAX (BCL2-associated X protein) and p21 expression by interfering with the interaction between SMARCD1 and p53, thereby reducing caspase3 cleavage and the downstream apoptosis cascades. We found that although SMARCD1 sensitized lung cancer cells to chemotherapy drug-induced apoptosis, miR-7 enhanced the drug resistance potential of lung cancer cells against chemotherapy drugs. SMARCD1 was down-regulated in patients with non-small cell lung cancer and lung adenocarcinoma cell lines, and SMARCD1 and miR-7 expression levels were negatively correlated in clinical samples. Our investigation into the involvement of the EGFR-regulated microRNA pathway in the SWI/SNF chromatin remodeling complex suggests that EGFR-mediated miR-7 suppresses the coupling of the chromatin remodeling factor SMARCD1 with p53, resulting in increased chemo-resistance of lung cancer cells. 

Retracted: Yes

PubPeer comments:
 The flow cytometry dot plots in red boxes appear to look similar in Fig 5D and 5F. ![file] The flow cytometry dot plots in red boxes appear to look similar in Fig 3G and 4F, but different gated percentages. ![file] , 
 Blue boxes: The immunoblot for different groups appear to look similar in Fig.3F,4E and 5A ![file] , 
 Thank you for reading and checking this article. I am the first author, Hong CF. To study the effects of miR-7 overexpression plus SCD1 p53 silencing, the cells in Figure 3, 4 and 5 were transduced with two lentiviral vectors (HR -puro for overexpression and PLKO.1 for silencing). These experiments were performed at the same time for comparison. Thus, in Figure 5D and 5F, control H1975 were H1975 cells transduced with both control HR -puro and scramble PLKO.1 and should be labeled as H1975-Ctrl scramble. Likewise, in Fig. 3G and 4F control A549 and H1975 cells were A549 and H1975 cells transduced with both control HR -puro and scramble PLKO.1 and labeled as A549-Ctrl scramble and H1975-Ctrl scramble. After carefully checking the immunoblotting data, I find the band is correct for p53 staining in H1975+cisplatin in Figure 3F, and photos in Fig. 4E and 5A were inadvertently misplaced during the submission. We will send the correction request to the journal for correcting unclear figure legends and misplaced photos. I thank you again for pointing out these errors and apology for shortcomings in this manuscript. , 
 2020 retraction. https: www.jbc.org content 295 52 18649 VOLUME 291 (2015) PAGES 1877u20131889 This article has been withdrawn by all the authors. The Journal pointed out that the p53 immunoblot from H1975 in Fig. 3F was reused in Fig. 4E (u03b1-tubulin) and Fig. 5A (p53 from A549), representing different experimental conditions. There are duplicated immunoblots representing different experimental conditions in the last column of Fig. 4B (u03b1-tubulin) and first column of Fig 5E. There is a duplicated FACS plot in Fig. 3G (H1975 scramble) and Fig. 4F (H1975 ctrl). There is a duplicated FACS plot in Fig. 5D (H1975 scramble) and Fig. 5F (ctrl). There are some duplicated immunoblots in Fig. 2A (A549 SMARDC1) and Fig. 4A (SMARDC1 column 1) as well as duplications with their respective u03b1-tubulin loading controls. The authors state that the errors occurred during preparation of the figures and figure legends and state that all of the results reported in this article are valid. Through a full discussion, all authors agree on the decision to withdraw the paper. ,