Expression and effect of let-7a, miR-21 and miR-27a in oral squamous cell carcinomas

doi:10.16098/j.issn.0529-1356.2015.02.013

Abstract

Abstract:

Objective To explore the expression and function of let-7a, miR-21 and miR-27a in oral squamous cell carcinomas(OSCCs). Methods Using in situhybridization by digmarked miRCURY LNATM microRNA detection probes, the expressions levels of let-7a, miR-21 and miR-27a were studied on nature and localization in 5 normal oral mucous tissues, 30 OSCCs and their paired pericarcinomatous tissues. The results of microRNAs expression were semi-quantitatively analyzed by image analysis. Results The expressions of let-7a, miR-21 and miR-27a were weak, and only found in 40%(2/5), 80% (4/5) and 40%(2/5) normal oral mucous tissues, respectively. But all the tumor tissues and their pericarcinomatous tissues expressed the three miRNAs in different extent. The expression levels of three miRNAs in OSCCs were much higher than that in pericarcinomatous tissues and normal tissues (P<0.01). The expression of let-7a and miR-27a in pericarcinomatous tissues was obviously higher than that in normal tissues (P<0.01), however, no obvious difference was observed between the expression of miR-21 in pericarcinomatous tissues and in normal tissues (P>0.05). No significant difference was detected in OSCC patients with different age and sex, and lymphatic metastasis or not (P>0.05). The expression of miR-27a in moderate/low differentiated OSCCs was higher than its expression in high differentiated OSCCs（P<0.05）. No statistical difference of miR-21 and let-7a expression was found in differentiation-different OSCCs (P>0.05). Correlation analysis showed that there was positive correlation between expression of let-7a and miR-21 in OSCCs, but no correlation was found between expression of miR-27a and let7a/miR-21.
Conclusion The overexpression patterns of let-7a, miR-21 and miR-27a play a certain role in tumorgenesis and development of OSCCs. miR-27a is an expected molecular marker associated with differentiated degree of OSCCs. There is a certain relation between let-7a and miR-21 in OSCCs.

Key words: Oral squamous cell carcinomas, let-7a, miR-21, miR-27a , In situ hybridization, Image analysis, Human

LIU Nai-guo* ZHANG Wei-qun HU Feng-ai WU Shu-hua- ZHU Yu-hong. Expression and effect of let-7a, miR-21 and miR-27a in oral squamous cell carcinomas[J]. AAS, 2015, 46(2): 221-226.

References

［1］Wiklund ED, Gao S, Hulf T, et al. MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma ［J］. PLoS One, 2011, 6(11):e27840.
［2］Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family ［J］. Cell, 2005,120（5）: 635-647. 
［3］Sampson VB, Rong NH, Han J, et al. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in burkitt lymphoma cells ［J］. Cancer Res, 2007, 67（20）: 9762-9770. 
［4］Brito JAR, Gomes CC, Pimenta FJGS, et al. Reduced expression of miR15a in the blood of patients with oral squamous cell carcinoma is associated with tumor staging ［J］. Exp Ther Med, 2010, 1（1）: 217-221.
［5］Yu CC, Chen YW, Chiou GY, et al. MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation ［J］. Oral Oncol, 2011, 47（3）: 202-210.
［6］Cervigne NK, Reis PP, Machado J, et al. Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma ［J］. Hum Mol Genet, 2009, 18（24）: 4818-4829.
［7］Li J, Huang H, Sun L, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor ［J］. Clin Cancer Res, 2009, 15（12）: 3998-4008.
［8］Zhao X, Yang Li, Hu J. Down-regulation of miR-27a might inhibit proliferation and drug resistance of gastric cancer cells ［J］. J Exp Clin Cancer Res, 2011, 30（1）:55. 
［9］Venkatesh T, Nagashri MN, Swamy SS, et al. Primary microcephaly gene MCPH1 shows signatures of tumor suppressors and is regulated by miR-27a in oral squamous cell carcinoma ［J］. PLoS One, 2013, 8(3):e54643.
［10］Stenvang J, Silahtaroglu AN, Lindow M, et al. The utility of LNA in microRNA-based cancer diagnostics and therapeutics ［J］. Semin Cancer Biol, 2008,18(2):89-102. 
［11］Liu NG, Wu ShH, Shan ChM, et al. The amplification and expression of c-erbB2 and p53 in oral squamous cell carcinomas ［J］. Acta Anatomica Sinica, 2003, 34(4):384-389. (in Chinese)
刘乃国，吴淑华，单长民，等. 口腔鳞癌中c-erbB2和P53基因的扩增和表达［J］. 解剖学报,2003,34(4):384-389.
［12］Gome CC, Sous SF,Gomez RS. MicroRNAs: small molecules with a potentially role in oral squamous cell carcinoma［J］.Curr Pharm Des, 2013, 19(7):1285-1291.
［13］Kim SJ, Shin JY, Lee KD, et al. MicroRNA let-7a suppresses breast cancer cell migration and invasion through down regulation of C-C chemokine receptor type 7 ［J］. Breast Cancer Res, 2012, 14（1）：R14.
［14］Wang YY, Ren T, Cai YY, et al. MicroRNA let-7a inhibits the proliferation and invasion of non-small cell lung cancer cell line 95D by regulating K-Ras and HMGA2 gene expression ［J］. Cancer Biother Radio Pharm，2013,28（2）：131-137.
［15］Zhang Z, Huang L, Yu Z，et al. Let-7a functions as a tumor suppressor in Ewing's sarcoma cell lines partly by targeting cyclin-dependent kinase 6［J］. DNA Cell Biol,2014,33(3):136-147.
［16］Lu L, Katsaros D, Zhu Y, et al. Let-7a regulation of insulin-like growth factors in breast cancer ［J］. Breast Cancer Res Treat, 2011,126 (3):687-694.
［17］Yang CH, Yue J, Pfeffer SR, et al. MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3) ［J］. J Biol Chem, 2014, 289(36):25079-25087. 
［18］Si ML, Zhu S, Wu H, et al. miR-21-mediated tumor growth ［J］. Oncogene, 2007, 26（19）: 2799-2803.
［19］Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer ［J］. Gastroenterology, 2007, 133（2）:647-658.
［20］Reis PP, Tomenson M, Cervigne NK,et al. Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma ［J］. Mol Cancer, 2010, 9:238
［21］Fletcher CE, Dart DA, Sita-Lumsden A, et al. Androgen-regulated processing of the oncomir miR-27a, which targets prohibitin in prostate cancer［J］. Hum Mol Genet, 2012, 21(14):3112-3127.
［22］Ma Y, Yu S, Zhao W, et al. miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2 ［J］. Cancer Lett, 2010, 298(2):150-158.

[1]	LIU Xiao-li XU Lin WU Ai-xue WEN Cai-yun LI Ru-hua WU An-ting CHEN Dai-qian CHEN Cheng-chun. Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica [J]. Acta Anatomica Sinica, 2024, 55(1): 17-24.
[2]	BAI He TENG Ye FENG Lei MENG Hai-wei1 TANG Yu-chun LIU Shu-wei. 3D hippocampal segmentation based on spatial and frequency domain features adaptive fusion and inter-class boundary region enhancement [J]. Acta Anatomica Sinica, 2024, 55(1): 73-81.
[3]	YIN Shi-qin YANG Si-yi WANG Rui-han YOU Gui-xuan YANG Ying-qiu ZHANG Lei. Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT [J]. Acta Anatomica Sinica, 2024, 55(1): 82-87.
[4]	YANG Yang SHI Jun LI Kun MA Yuan ZHANG Shao-jie HOU Er-fei WANG Chao-qun CHEN Jie WANG Xing LI Zhi-jun. Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes [J]. Acta Anatomica Sinica, 2024, 55(1): 88-97.
[5]	SUN Lei WANG Xing-yu XIE Shui-hua. Risk analysis of re-fracture after percutaneous kyphoplasty in elderly patients with osteoporotic thoracolumbar compression fractures and construction of acolumnar graph prediction model#br# [J]. Acta Anatomica Sinica, 2024, 55(1): 98-104.
[6]	LIU Li-ping ZHU Meng-ni XU Hui . Effect of interleukin-6 on nucleated erythrocytes in lipopolysaccharide induced preeclampsia rats [J]. Acta Anatomica Sinica, 2023, 54(6): 722-729.
[7]	ZHAO Wei-ming LI Xiao YU Guo-ying WANG Gai-ping CHANG Cui-fang . Effect of serine protease inhibitor Kazaltype 1 on the proliferation of hepatocellular carcinoma cell and its mechanism [J]. Acta Anatomica Sinica, 2023, 54(6): 695-702.
[8]	HAN Yi CAI Li FENG Xiao . Risk analysis of bone cement leakage after percutaneous puncture vertebroplasty for osteoporotic spinal compression fractures and construction of a predictive model with column line drawings [J]. Acta Anatomica Sinica, 2023, 54(6): 710-715.
[9]	DU Da-peng SUN Yu ZHANG Min WANG Han-qin . Shear stress regulateing the phosphorylation of endothelial nitric oxide synthase Ser633 and Ser1177 in human umbilical vein endothelial cells through Pim1/Akt pathway [J]. Acta Anatomica Sinica, 2023, 54(5): 546-552.
[10]	ZHOU Chun-hui XIE Sheng-qiang WANG Jiang-ting LAN Xiao-juan ZHANG Jian-ning ZHAO Hu-lin . Application of multimodal electromagnetic navigation in endoscopic endonasal skull base anatomical measurement of fresh cadavers [J]. Acta Anatomica Sinica, 2023, 54(5): 560-566.
[11]	LIU Yan-jing SHI Yong-hong . Automatic extraction of point cloud on cartilage surface of intraoperative knee using FPFH-PointNet [J]. Acta Anatomica Sinica, 2023, 54(5): 553-559.
[12]	MI Si-rong LIU Guang-xing ZHANG Zhen-wu YU Peng-hui JU Xiao-jun RAO Li-bing LI Li . Accuracy of 3D printing skull under different CT layer thickness [J]. Acta Anatomica Sinica, 2023, 54(5): 575-581.
[13]	ZHU Qiu-liang YU Xiang-ping MA Jun CHEN Yun-yun LIN Fang RUAN Wen-bin . Adjustment of X-ray angle intraoperation based on the anatomic shape of femoral neck section [J]. Acta Anatomica Sinica, 2023, 54(5): 586-592.
[14]	LI Xiao-jun ZHANG Ya-min. Screening ferroptosis related genes influencing prognosis of colon cancer through bioinformatics analysis [J]. Acta Anatomica Sinica, 2023, 54(4): 445-452.
[15]	LIU Hai-lan MEI Yi-xuan ZHANG Yi LIU Cheng LIU Shu-wei. Classification and clinical significance of the branching patterns of the right pulmonary arteries based on the intravital CT data [J]. Acta Anatomica Sinica, 2023, 54(4): 453-459.