MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion
Authors: Xin Xu
Zhaoyuan Li
Jin Liang
Qibao Wang
Yi Du
Lanying Sun
Journal: Cell Proliferation (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tongue squamous cell carcinoma; miR-137; TSCC; proliferation; invasion
Affiliations: School of Stomatology, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, 250012, China., Oral Implantology Center, Stomatology Hospital of Jinan, Jinan, 250001, China., Department of Endodontics, Stomatology Hospital of Jinan, Jinan, 250001, China., School of Stomatology, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, 250012, China. .

Abstract:  Objectives: Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral malignancy. Increasing evidence has shown that miRNAs play key roles in many biological processes such as cell development, invasion, proliferation, differentiation, metabolism, apoptosis and migration. Materials and methods: qRT-PCR analysis was performed to measure miR-137 expression. CCK-8 analysis, cell colony formation, wound-healing analysis and invasion were performed to detect resultant cell functions. The direct target of miR-137 was labelled and measured by luciferase assay and Western blotting. Results: We demonstrated that expression of miR-137 was downregulated in TSCC tissues compared to matched normal ones. miR-137 expression was downregulated in TSCC lines (SCC4, SCC1, UM1 and Cal27) compared to the immortalized NOK16B cell line and normal oral keratinocytes in culture (NHOK). In addition, we have shown that miR-137 expression was epigenetically regulated in TSCCs. Overexpression of miR-137 suppressed TSCC proliferation and colony formation. Ectopic expression of miR-137 promoted expression of the epithelial biomarker, E-cadherin, and inhibited the mesenchymal biomarker, N-cadherin, as well as vimentin and Snail expression, indicating that miR-137 suppressed TSCC epithelial-mesenchymal transition (EMT). We also showed that ectopic expression of miR-137 inhibited TSCC invasion and migration. In addition, we identified SP1 as a direct target gene of miR-137 in SCC1 cells. SP1 overexpression rescued inhibitory effects exerted by miR-137 on cell proliferation and EMT. Conclusions: These results indicate that miR-137 acted as a tumour suppressor in TSCC by targeting SP1. 

Retracted: No

PubPeer comments:
 Fig 5  (D) FITC-L-PHA binding profiles of MCF ADR cells using flow cytometry. Histograms of fluorescence intensities of cells with specific carbohydrate expression as determined . Fig 6  (D) FITC-L-PHA binding profiles of MCF-7 cells using flow cytometry. Histograms of fluorescence intensities of cells with specific carbohydrate expression as determined . ![file] Two pairs of panels match unexpectedly well after stretching the 6D versions. Is this normal for flow-cytometry histograms? , 
 The GAPDH panel of Fig 5A [below] bears comparison with [above] Fig 6B from  B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562 adriamycin-resistant cell line [(Zhou et al 2012)] . The first lane, anyway. ![file] , 
 Figure 6.  (A) MCF-7 cells were transfected with a pcDNA3.1 expression vector, and Western blot analysis for MGAT5 was assessed. GAPDH was also examined and served as controls for sample loading [above]. [Below]: Figure 5  (A) After K562 ADR cells were transfected with ... ST8SIA4 siRNA for 30 h, western blot analysis for ... ST8SIA4 were assessed. GAPDH was also examined and served as controls for sample loading . From  Glycomic alterations are associated with multidrug resistance in human leukemia [(Zhang et al 2012)] . ![file] Could the authors specify under which conditions the GAPDH blot was obtained? Update: A third sighting of this slice (notable for the lipstick lane at right) in Fig 5B of [Guo et al (2013)] . ![file] , 
 **Decision on handling misconduct cases investigated and handled in 2021 (third batch)** https: www.nsfc.gov.cn publish portal0 tab434 info81957.htm This paper is discussed among the 22 handling decisions announced by the National Natural Science Foundation of China u201cthat have been criticized for notification are now published.u201d (Google Translate). , 
 #4 Have the journal s editors considered their position on this paper? **Regarding the problem of image duplication and rotation in the papers published by Jia Li et al. And provide false information in the project application, progress final report** **Processing decision** National Science and Technology Supervision Office (2021) No. 78 The Supervision Committee of the National Natural Science Foundation of China launched an investigation into the suspected academic misconduct in the papers published by Jia Li of Dalian Medical University. The papers involved are as follows: - Paper 1:  Li Jia, Huimin Zhou, Shujing Wang, Jun Cao, Wei Wei, Jianing Zhang*. Deglycosylation of CD147 down-regulates Matrix Metalloproteinase-11 expression and the adhesive capability of murine hepatocarcinoma cell HcaF in vitro. IUBMB Life, 2006 , 58(4):209-216.u201d (marked with fund number 30470400) - Paper 2:  Li Jia, Shujing Wang, Jun Cao, Huimin Zhou, Wei Wei, Jianing Zhang*. siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell HcaF to lymph nodes. The International Journal of Biochemistry uff06 Cell Biology , 2007, 39(11): 2049-2062.u201d (marked with fund numbers 30470400, 30670466) - Paper 3:  Li Jia, Huaxin Wang, Shuxian Qu, Xiaoyan Miao, Jianing Zhang*. CD147 regulates vascular endothelial growth factor-A expression, tumorigenicity, and chemosensitivity to curcumin in hepatocellular carcinoma. IUBMB Life, 2008, 60(1): 57-63.u201d (marked with fund numbers 30470400, 30670466) - Paper 4:  Li Jia, Henggui Xu, Yongfu Zhao, Lili Jiang, Jingda Yu, Jianing Zhang*. Expression of CD147 Mediates Tumor Cells Invasion and Multidrug Resistance in Hepatocellular Carcinoma. Cancer Investigation, 2008, 26(10):977-983 . (marked with fund number 30670466) - Paper 5:  Li Jia, Wei Wei, Jun Cao, Henggui Xu, Xiaoyan Miao, Jianing Zhang*. Silencing CD147 inhibits tumor progression and increases chemosensitivity in murine lymphoid neoplasm P388D1 cells. Annals of Hematology, 2009, 88(8):753 -760. (marked with fund number 30670466) - Paper 6:  Zhaohai Zhang # , Yongfu Zhao # , Lili Jiang, Xiaoyan Miao, Huimin Zhou, Li Jia*. Glycomic alterations are associated with multidrug resistance in human leukemia. The International Journal of Biochemistry uff06 Cell Biology, 2012, 44(8 ):1244-1253.u201d (marked with fund number 8107415) - Paper 7:  Huimin Zhou, Zhaohai Zhang, Chunqing Liu, Changgong Jin, Jianing Zhang, Xiaoyan Miao, Li Jia*. B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562 adriamycin-resistant cell line. IUBMB Life, 2012, 64(11):889-900.u201d (marked with fund number 81071415) - Paper 8:  RuiGuo # , Lei Cheng # , Yongfu Zhao, Jianing Zhang, Chunqing Liu, Huimin Zhou, Li Jia*. Glycogenes mediate the invasive properties and chemosensitivity of human hepatocarcinoma cells. The International Journal of Biochemistry Cell Biology, 2013, 45(2):347-358.u201d (marked with fund number 81071415) - **Paper 9:  Hongye Ma # , Xiaoyan Miao # , Qiuhong Ma, Wenzhi Zheng, Huimin Zhou, Li Jia. Functional roles of glycogene and N-glycan in multidrug resistance of human breast cancer cells. IUBMB Life, 2013, 65(5 ): 409-422.u201d (marked with fund number 81071415)** - Paper 10:  Zhaohai Zhang # , Jie Sun # , Lihong Hao, Chunqing Liu, Hongye Ma, Li Jia*. Modification of Glycosylation Mediates the Invasive Properties of Murine Hepatocarcinoma Cell Lines to Lymph Nodes. PLoS One, 2013, 8(6) :e65218.u201d (marked with fund numbers 81071415, 81271910) - Paper 11:  Hongye Ma # , Lei Cheng # , Keji Hao, Yanping Li, Xiaobo Song, Huimin Zhou, Li Jia*. Reversal Effect of ST6GAL1 on Multidrug Resistance in Human Leukemia by Regulating the PI3K Akt Pathway and the Expression of P -gp and MRP1. PLoS One, 2014, 9(1):e85113.u201d (marked with fund numbers 81071415, 81271910) - Paper 12:  Hongye Ma # , Huimin Zhou # , Peng Li, Xiaobo Song, Xiaoyan Miao, Yanping Li, Li Jia*. Effect of ST3GAL4 and FUT7 on sialyl Lewis X synthesis and multidrug resistance in human acute myeloid leukemia. Biochimica et Biophysica Acta, 2014, 1842(9):1681-1692.u201d (marked with fund number 81271910) - Paper 13:  Yongfu Zhao, Yanping Li, Hongye Ma, Weijie Dong, Huimin Zhou, Xiaobo Song, Jianing Zhang, Li Jia*. Modification of Sialylation Mediates the Invasive Properties and Chemosensitivity of Human Hepatocellular Carcinoma. Molecular and Cellular Proteomics, 2014, 13(2):520-536.u201d (marked with fund numbers 81071415, 81271910) - Paper 14:  Lei Cheng # , Shuhang Gao # , Xiaobo Song, Weijie Dong, Huimin Zhou, Lifen Zhao, Li Jia*. Comprehensive N-glycan profiles of hepatocellular carcinoma reveal association of fucosylation with tumor progression and regulation of FUT8 by microRNAs. Oncotarget, 2016, 7(38):61199-61214.u201d (marked with fund numbers 81271910, 81472014) - Paper 15:  Jialei Hu # , Zi Wang # , Yujia Shan, Yue Pan, Jia Ma, Li Jia*. Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p FUT2 u03b2-catenin axis. Cell Death and Disease, 2018, 9(7):711.u201d (labeled fund number 81772277) After investigation, the above-mentioned papers have problems such as photo duplication and rotation. As the corresponding author of papers 7, 8, 9, 10, 11, 12, 14, 15 and the first author of papers 1, 2, 3, 4, and 5, Jia Li is mainly responsible for the misconduct of papers 6, 13 The behavior bears secondary responsibility. The papers 1, 2, 3, 4, 5, and 6 are also listed in the application form of the National Natural Science Foundation of China (approval number 81271910), and the papers 2, 3, 4, and 5 are listed in the country In the application form of the Natural Science Foundation Project (approval number 81071415), the papers 6, 7, 8, 9, 10, 11, and 13 are listed in the application form of the National Natural Science Foundation Project (approval number 81472014), and the papers 6, 7 , 8, 9, 10, 11, 13, and 14 were included in the application of the National Natural Science Foundation of China (approval number 81772277), and the papers 6, 7, 8, 9, 13 were included in the National Natural Science Foundation of China (approved No. 81071415) In the progress report, Papers 10, 11, and 13 are included in the progress report of the National Natural Science Foundation of China (approval number 81271910), and Paper 14 is included in the progress report of the National Natural Science Foundation of China (approval number 81472014) , Included papers 6, 7, 8, 9, 10, and 11 in the final report of the National Natural Science Foundation of China (approval number 81071415), and included papers 10, 11, and 14 in the National Natural Science Foundation of China (approval number) 81271910) in the final report. After deliberation at the 10th meeting of the 5th Supervisory Committee of the National Natural Science Foundation of China (Life Medicine Professional Committee), and approved by the 13th Executive Meeting of the National Natural Science Foundation of China in 2021, it was decided to comply with the 35th National Natural Science Foundation Regulation Article 4,  The National Natural Science Foundation of China Supervision Committee s Measures for Handling Misconduct in the Funding of Science (for Trial Implementation) Article 16, Paragraph 2 and Article 17, Paragraph 3, revoke Jia Li The National Natural Science Foundation of China project  Exploration of glycoprotein N-sugar chain as a marker for predicting tumor resistance (approval number 81071415),  Characteristic changes of glycogenes in leukemia multidrug resistance and its diagnostic value (approved No. 81271910),  Screening, identification and functional study of leukemia drug-resistant sugar complex markers (Approval No. 81472014),  Screening of carbohydrate markers for liver metastasis of colorectal cancer (Approval No. 81772277), withdrawn Funds have been allocated for the above four projects, and Jia Liu2019s national natural science fund project application qualification has been cancelled for 5 years (July 20, 2021 to July 19, 2026), and Jia Li has been criticized in a circular. National Natural Science Foundation of China September 19, 2021 ,