IGF2BP2的异常表达影响口腔鳞状细胞癌的增殖和侵袭

doi:10.13701/j.cnki.kqyxyj.2021.04.017

口腔医学研究 ›› 2021, Vol. 37 ›› Issue (4): 354-359.DOI: 10.13701/j.cnki.kqyxyj.2021.04.017

IGF2BP2的异常表达影响口腔鳞状细胞癌的增殖和侵袭

胡雅英^1,2, 陈文³, 张佳莉^1,2*

1.武汉大学口腔医院口腔病理科湖北武汉 430079;
2.口腔基础医学省部共建国家重点实验室培育基地和口腔生物医学教育部重点实验室武汉大学口腔医学院湖北武汉 430079;
3.武汉生命之美科技有限公司基因组分析中心湖北武汉 430075

收稿日期:2020-09-02 发布日期:2021-04-15
通讯作者: *张佳莉,E-mail: jiali_zhang@whu.edu.cn
作者简介:胡雅英(1993~ ),女,湖北武汉人,硕士在读,主要从事口腔肿瘤的研究。
基金资助:
国家自然科学基金(编号:8197103262)

Aberrant Expression of IGF2BP2 Promotes Proliferation and Invasion of Oral Squamous Cell Carcinoma

HU Yaying^1,2, CHEN Wen³, ZHANG Jiali^1,2*

1. Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
2. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School of Stomatology, Wuhan University. Wuhan 430079, China;
3. Center for Genome Analysis, ABLife Inc, Wuhan 430075, China

Received:2020-09-02 Published:2021-04-15

摘要/Abstract

摘要： 目的: 探讨口腔鳞状细胞癌(OSCC)中异常表达的胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)对增殖和侵袭的影响。方法: 将4对OSCC组织及癌旁组织进行mRNA高通量测序,筛选差异表达RNA结合蛋白;在OSCC细胞系中利用RNA干扰沉默技术降低IGF2BP2的表达;利用CCK-8和Transwell实验检测IGF2BP2对增殖和侵袭的影响。对HSC3细胞系进行改良RIP高通量测序(Improved RIP-seq, iRIP-seq)和mRNA高通量测序分析IGF2BP2的下游靶基因,运用KEGG信号通路富集分析获得IGF2BP2靶标基因的主要富集信号通路。结果: 在OSCC癌组织中IGF2BP2为表达丰度和差异上调最为显著的RNA结合蛋白(P=7.11E-06)。下调IGF2BP2抑制OSCC的体内外增殖和体外侵袭。IGF2BP2的潜在靶标基因主要富集到Axon guidance、 Focal adhesion、Rap1信号通路、pathways in cancer、MAPK信号通路等。结论: IGF2BP2在OSCC中表达增高并可能通过影响细胞增殖和粘附相关信号通路发挥促进肿瘤的作用。

关键词: 胰岛素样生长因子2 mRNA结合蛋白2, 口腔鳞状细胞癌, 增殖, 侵袭

Abstract: Objective: To explore the effects of aberrant expressed IGF2BP2 on proliferation and invasion of oral squamous cell carcinoma (OSCC). Methods: High-throughput RNA sequencing was performed on four pairs of OSCC tissues and adjacent normal tissues to screen differentially expressed RNA binding proteins. siRNA was used to reduce the expression of IGF2BP2 in OSCC cell lines. The effects of IGF2BP2 on proliferation and invasion were determined by CCK-8 and Transwell Assay. The target genes of IGF2BP2 were analyzed by Improved RIP-seq and mRNA-seq, and the main signal pathways of IGF2BP2 target genes were obtained by KEGG analysis. Results: The abundance and up-regulation of IGF2BP2 was the most significantly in the RNA-binding proteins in OSCC (P<0.01). The decreased IGF2BP2 inhibited the proliferation and invasion of OSCC cell lines. The target genes of IGF2BP2 were mainly enriched in Axon Guidance, Focal expression, Rap1 signaling pathway, Pathways in Cancer, and MAPK signaling pathway. Conclusion: IGF2BP2 is increased in OSCC and may promote tumor progression by affecting cell proliferation and adherence-related signaling pathways.

Key words: IGF2BP2, OSCC, proliferation, invasion

胡雅英, 陈文, 张佳莉. IGF2BP2的异常表达影响口腔鳞状细胞癌的增殖和侵袭[J]. 口腔医学研究, 2021, 37(4): 354-359.

HU Yaying, CHEN Wen, ZHANG Jiali. Aberrant Expression of IGF2BP2 Promotes Proliferation and Invasion of Oral Squamous Cell Carcinoma[J]. Journal of Oral Science Research, 2021, 37(4): 354-359.

参考文献

[1] Bell JL, Wächter K, Mühleck B, et al. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression? [J]. Cell Mol Life Sci, 2013, 70(15): 2657-2675.
[2] Lunde BM, Moore C, Varani G. RNA-binding proteins: modular design for efficient function [J]. Nat Rev Mol Cell Biol, 2007, 8(6): 479-490.
[3] Huang H, Weng H, Sun W, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation [J]. Nat Cell Biol, 2018, 20(3): 285-295.
[4] Cao J, Mu Q, Huang H. The roles of insulin-like growth factor 2 mRNA-binding protein 2 in cancer and cancer stem cells [J]. Stem Cells Int, 2018, 2018:4217259.
[5] Dahlem C, Barghash A, Puchas P, et al. The insulin-like growth factor 2 mRNA binding protein IMP2/IGF2BP2 is overexpressed and correlates with poor survival in pancreatic cancer [J]. Int J Mol Sci, 2019, 20(13): 3204.
[6] Wang Y, Lu JH, Wu QN, et al. LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer [J]. Mol Cancer, 2019, 18(1): 174.
[7] Mu Q, Wang L, Yu F, et al. Imp2 regulates GBM progression by activating IGF2/PI3K/Akt pathway [J]. Cancer Biol Ther, 2015, 16(4): 623-633.
[8] Deng X, Jiang Q, Liu Z, et al. Clinical significance of an m6A reader gene, IGF2BP2, in head and neck squamous cell carcinoma [J]. Front Mol Biosci, 2020, 7:68.
[9] Gerstberger S, Hafner M, Tuschl T. A census of human RNA-binding proteins [J]. Nat Rev Genet, 2014, 15(12): 829-845.
[10] Qin H, Ni H, Liu Y, et al. RNA-binding proteins in tumor progression [J]. J Hematol Oncol, 2020, 13(1): 90.
[11] Dai N, Zhao L, Wrighting D, et al. IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1 mRNA and Other mRNAs encoding mitochondrial proteins [J]. Cell Metab, 2015, 21(4): 609-621.
[12] Dai N, Ji F, Wright J, et al. IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1 [J]. Elife, 2017, 6:e27155.
[13] Zhou X, Wu X, Qin L, et al. Anti-breast cancer effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione in vivo and in vitro through MAPK signaling pathway [J]. Drug Des Devel Ther, 2020, 14:2667-2684.
[14] Ye K, Ouyang X, Wang Z, et al. SEMA3F promotes liver hepatocellular carcinoma metastasis by activating focal adhesion pathway [J]. DNA Cell Biol, 2020, 39(3): 474-483.
[15] Zhou S, Liang Y, Zhang X, et al. SHARPIN promotes melanoma progression via Rap1 signaling pathway [J]. J Invest Dermatol, 2020, 140(2): 395-403.e6.
[16] Sorber R, Teper Y, Abisoye-Ogunniyan A, et al. Whole genome sequencing of newly established pancreatic cancer lines identifies novel somatic mutation (c.2587G>A) in axon guidance receptor plexin A1 as enhancer of proliferation and invasion [J]. PLoS One, 2016, 11(3): e0149833.

IGF2BP2的异常表达影响口腔鳞状细胞癌的增殖和侵袭

Aberrant Expression of IGF2BP2 Promotes Proliferation and Invasion of Oral Squamous Cell Carcinoma

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张旭, 刘佳文. MMP-9、COX-2、NF-κB在口腔鳞状细胞癌组织中的表达及意义[J]. 口腔医学研究, 2021, 37(4): 360-365.
[2]	尹芳, 李进杰, 龚平, 周腾鹏, 刘可斌, 张铁军. 两种全麻方法对口腔鳞癌患者免疫功能影响的比较研究[J]. 口腔医学研究, 2021, 37(2): 153-156.
[3]	关孟莹, 何丽娜, 潘爽, 李艳萍, 刘会梅, 牛玉梅. 经典Wnt信号通路对hDPSCs增殖、迁移和成牙本质向分化的影响[J]. 口腔医学研究, 2020, 36(9): 861-865.
[4]	邱吟枫, 汤颖, 沈忆芬, 刘超, 沈昊, 顾永春, 于金华. 氟暴露对人牙周膜干细胞增殖及成骨分化的影响[J]. 口腔医学研究, 2020, 36(9): 866-870.
[5]	陈振宇, 潘颖菁, 张艳, 贺玺, 黄达鸿. 葛根素对高浓度糖皮质激素环境下MC3T3-E1前成骨细胞生物学性能的影响[J]. 口腔医学研究, 2020, 36(6): 544-547.
[6]	尚佳鑫, 苏瑞, 马冲, 李新月. 两种抛光方式对两种充填材料表面形貌和细胞增殖能力的影响[J]. 口腔医学研究, 2020, 36(6): 581-584.
[7]	高安天, 林梓桐. 口腔鳞状细胞癌边界精准评价的光学成像研究进展[J]. 口腔医学研究, 2020, 36(5): 413-415.
[8]	杨凯成, 杨蕾, 赵建广, 罗风玉, 陈彦平, 崔子峰, 陈赫, 满莎莎. 口腔鳞状细胞癌患者外周血microRNA的表达及预后意义[J]. 口腔医学研究, 2020, 36(5): 428-432.
[9]	周伟, 汤雅, 李厚轩. 南京地区侵袭性牙周炎近6年就诊情况调查分析[J]. 口腔医学研究, 2020, 36(5): 473-476.
[10]	王薛藤, 聂敏海, 左东川, 邓浩, 曾锦. TRPM4通道对人口腔颊黏膜成纤维细胞增殖和迁移的影响[J]. 口腔医学研究, 2020, 36(5): 490-495.
[11]	胡勤刚, 赵星星. 口腔鳞状细胞癌肿瘤相关成纤维细胞的研究进展[J]. 口腔医学研究, 2020, 36(4): 309-313.
[12]	殷晓薇, 张爽, 邓皓天, 何丽娜, 李艳萍, 张巍巍, 潘爽, 牛玉梅. 整合素α6对hDPSCs增殖和成牙本质向分化的影响[J]. 口腔医学研究, 2020, 36(12): 1132-1136.
[13]	郭俊峰, 张纲, 谭颖徽. CYP27B1在口腔鳞状细胞癌中的表达及其与预后的关系[J]. 口腔医学研究, 2020, 36(10): 930-933.
[14]	张维甲, 潘爽, 李艳萍, 何丽娜, 吴作栋, 牛玉梅. 兔牙髓干细胞与雪旺细胞体外间接共培养对增殖和兔牙髓干细胞成神经向分化的研究[J]. 口腔医学研究, 2020, 36(10): 968-972.
[15]	闫娜, 黄涛, 张中月, 张淑华, 王丽华, 韩国良. 富血小板纤维蛋白对牙髓干细胞增殖和成骨分化的功能研究[J]. 口腔医学研究, 2020, 36(10): 973-977.