Effect of SREBP2 on proliferation and migration of oral squamous cell carcinoma and its regulatory mechanism

doi:10.19438/j.cjoms.2021.04.002

Abstract

Abstract: PURPOSE: To investigate the effect of sterol regulatory element-binding protein 2 (SREBP2) on the malignant biological behaviors of oral squamous cell carcinoma (OSCC) cell lines. METHODS: The expression of SREBP2 in OSCC was detected by qRT-PCR. SiRNA and overexpression plasmids were constructed and transferred into CAL27. The ability of cell proliferation was detected by cell counting kit-8(CCK-8) assay and EdU cell-proliferation assay; the level of apoptosis was detected by flow cytometry; the ability of migration and invasion was detected by wound-healing assay and Transwell migration and invasion assays. Western blotting was used to detect the expression of SREBP2-related proteins. The data were plotted by Graphpad 5.0; Student's t tests were used to evaluate difference among groups. RESULTS: The expression of SREBP2 in 50 pairs of OSCC tissues and OSCC cell lines was significantly lower than that in normal controls. Knock-down and overexpression experiments showed that the change of SREBP2 expression affected the malignant biological behavior of OSCC cells and affected the development of OSCC through MVA signal pathway. CONCLUSIONS: SREBP2 inhibits proliferation, migration, invasion and promotes apoptosis of cancer cells in OSCC.

Key words: SREBP2, Oral squamous cell carcinoma, MVA signaling pathway, Proliferation, Migration

CLC Number:

R739.8

GUO Ming, CHEN Yu-ling, WU Li, ZHANG Bi-ru, SHEN Yue-hong, YANG Hong-yu. Effect of SREBP2 on proliferation and migration of oral squamous cell carcinoma and its regulatory mechanism[J]. China Journal of Oral and Maxillofacial Surgery, 2021, 19(4): 295-301.

References

[1] Neville BW, Day TA.Oral cancer and precancerous lesions[J]. CA Cancer J Clin, 2002, 52(4): 195-215.
[2] Vigneswaran N, Williams MD.Epidemiologic trends in head and neck cancer and aids in diagnosis[J]. Oral Maxillofac Surg Clin North Am, 2014, 26(2): 123-141.
[3] 陈洋, 尚政军. 自噬促进口腔鳞状细胞癌的上皮间质转化[J].口腔颌面外科杂志, 2020, 30(5): 285-287.
[4] Chi AC, Day TA, Neville BW.Oral cavity and oropharyngeal squamous cell carcinoma-an update[J]. CA Cancer J Clin, 2015, 65(5): 401-421.
[5] Majumdar B, Patil S, Sarode SC, et al.Clinico-pathological prognosticators in oral squamous cell carcinoma: an update[J]. Transl Res Oral Oncol, 2017, 2(1): 1-14.
[6] Ozturk K, Gode S, Erdogan U, et al.Squamous cell carcinoma of the lip: survival analysis with long-term follow-up[J]. Eur Arch Otorhinolaryngol, 2015, 272(11): 3545-3550.
[7] Scully C, Bagan J.Oral squamous cell carcinoma overview[J]. Oral Oncol, 2009, 45(4/5): 301-308.
[8] Bello IO, Soini Y, Salo T.Prognostic evaluation of oral tongue cancer: means, markers and perspectives (Ⅱ)[J]. Oral Oncol, 2010, 46(9): 636-643.
[9] Tan M, Myers JN, Agrawal N.Oral cavity and oropharyngeal squamous cell carcinoma genomics[J]. Otolaryngol Clin North Am, 2013, 46(4): 545-566.
[10] Ray U, Roy SS.Aberrant lipid metabolism in cancer cells-the role of oncolipid-activated signaling[J]. FEBS J, 2018, 285(3): 432-443.
[11] 王希明, 张晔, 邓明明, 等. 肿瘤相关异常脂质代谢研究进展[J]. 现代肿瘤医学, 2019, 27(21): 3906-3911.
[12] Pandyra A, Mullen PJ, Kalkat M, et al.Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop[J]. Cancer Res, 2014, 74(17): 4772-4782.
[13] Zhong C, Fan L, Li Z, et al.SREBP2 is upregulated in esophageal squamous cell carcinoma and co-operates with c-Myc to regulate HMGCR expression[J]. Mol Med Rep, 2019, 20(4): 3003-3010.
[14] 李晓枫, 刘展华. SREBP2在原发性肝癌中的表达水平与临床病理特征及预后的关系[J]. 热带医学杂志, 2019, 19(10): 1201-1204.
[15] Feng S, Han M, Zhou L, et al.NS5ABP37 inhibits liver cancer by impeding lipogenesis and cholesterogenesis[J]. Cancer Sci, 2017, 108(1): 12-22.
[16] Gentile CL, Frye MA, Pagliassotti MJ.Fatty acids and the endoplasmic reticulum in nonalcoholic fatty liver disease[J]. Biofactors, 2011, 37(1): 8-16.
[17] Thurnher M, Gruenbacher G. T lymphocyte regulation by mevalonate metabolism [J]. Sci Signal, 2015, 8(370): re4-re4.
[18] Johnson KJ, McDowell EN, Viereck MP, et al. Species-specific dibutyl phthalate fetal testis endocrine disruption correlates with inhibition of SREBP2-dependent gene expression pathways[J]. Toxicol Sci, 2011, 120(2): 460-474.
[19] Thurnher M, Gruenbacher G, Nussbaumer O.Regulation of mevalonate metabolism in cancer and immune cells[J]. Biochim Biophys Acta, 2013, 1831(6): 1009-1015.
[20] 邓嘉成. 葡萄糖介导SCAP的N-糖基化为SREBP-1激活和肿瘤生长所必需[J]. 生理科学进展, 2016, 47(2): 87-87.
[21] Santos CR, Schulze A.Lipid metabolism in cancer[J]. FEBS J, 2012, 279(15): 2610-2623.
[22] 王开, 朱炎, 刘玲珍, 等. 凋亡相关基因Bcl-2、Bax与舌鳞状细胞癌的相关性研究[J]. 口腔医学, 2009, 29(7): 337-339, 347.
[23] He Y, Shao F, Pi W, et al.Largescale transcriptomics analysis suggests over-expression of BGH3, MMP9 and PDIA3 in oral squamous cell carcinoma[J]. PLoS One, 2016, 11(1): e0146530.
[24] Heshiki W, Tomihara K, Yamazaki M, et al.Constitutive activation of caspase-3 in non-apoptotic oral squamous cell carcinoma cells[J]. J Cancer Sci Ther, 2015, 7(1): 75-80.
[25] Wang X, Jiang W, Duan N, et al.NOD1, RIP2 and Caspase12 are potentially novel biomarkers for oral squamous cell carcinoma development and progression[J]. Int J Clin Exp Pathol, 2014, 7(4): 1677-1686.