miR-30通过调节CD90表达抑制肝细胞肝癌

李培; 李莲; 郭燕; 郑红; 宋丰举; 刘奔; 陈可欣

doi:10.3969/j.issn.1000-8179.20141389

miR-30通过调节CD90表达抑制肝细胞肝癌

doi: 10.3969/j.issn.1000-8179.20141389

李培^{①, ②,},
李莲^①,
郭燕^①,
郑红^①,
宋丰举^①,
刘奔^①,
陈可欣^①, ,

①.
天津医科大学肿瘤医院，肿瘤研究所肿瘤分子流行病与生物统计研究室，国家肿瘤临床研究中心，天津市肿瘤防治重点实验室(天津市 300060)
②.
天津医科大学研究生院，肿瘤研究所肿瘤分子流行病与生物统计研究室，国家肿瘤临床研究中心，天津市肿瘤防治重点实验室(天津市 300060)

详细信息

作者简介:
李培专业方向为流行病与卫生统计学专业。E-mail：lipei19862011@163.com

通讯作者:
陈可欣 chenkexin@tijmu.edu.cn

计量
- 文章访问数: 14
- HTML全文浏览量: 36
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2014-05-09
- 修回日期: 2014-08-10
- 刊出日期: 2020-12-29

miR-30 functions as a tumor suppressor by modulating CD90 in hepatocellular carcinoma

LI Pei^{①, ②
,},
LI Lian^①,
GUO Yan^①,
ZHENG Hong^①,
SONG Fengju^①,
LIU Ben^①,
CHEN Kexin^{①
, ,}

①.
Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
②.
Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, The Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Key Laboratory of Cancer Prevention and Therapy, Graduate School, Tianjin Medical University, Tianjin 300070, China

More Information

Corresponding author: Kexin CHEN; E-mail: chenkexin@tijmu.edu.cn

摘要

摘要: 目的 miRNA能通过转录后调节靶基因的表达量，并在致癌过程中发挥抑癌或促癌作用。研究发现miR-30家族在人类肿瘤中起着重要作用，并参与维持干细胞特性的上皮细胞间质化过程，本研究主要识别miR-30家族与肝细胞肝癌的关系。方法应用qRT-PCR实验方法检测93例肝细胞肝癌患者癌组织和癌旁正常组织中miR-30c，miR-30b和miR-30e表达水平，另对121例肝细胞肝癌患者癌组织进行miR-30家族的表达及CD90免疫组织化学表达检测，分析miR-30家族与CD90在肝细胞肝癌中的相关性。结果本研究发现miR-30c(P < 0.001)、miR-30b(P=0.004)和miR-30e(P < 0.001)与癌旁正常组织相比，癌组织中表达显著下调。CD90蛋白在癌组织中的表达水平显著高于癌旁正常组织(P=0.007)。MiR-30c(P=0.032)和miR-30e(P=0.015)在CD90阴性表达的患者中表达水平显著高于CD90阳性表达的患者。结论 miR-30家族在肝细胞肝癌中可作为抑癌miRNA，并通过调节CD90蛋白来发挥这一作用。
- 肝细胞肝癌 /
- miR-30家族 /
- CD90 /
- 肿瘤干细胞 /
- 上皮细胞间质化
Abstract: Objective miRNA can post-transcriptionally regulate the expression of target genes and act as oncogenes or tumor suppressor genes in tumorigenesis. Emerging evidence demonstrates that the miR-30 family may perform an important function in human cancers and can regulate epithelial-mesenchymal transition, which has a critical role in cancer stem cells. This research was conducted to identify the possible association between the miR-30 family and hepatocellular carcinoma (HCC). Methods The expression of miR-30c, miR-30b, and miR-30e in 93 tumor tissues and adjacent tissues were measured by real-time reverse transcription PCR. Furthermore, 121 tumor tissues from an independent cohort were selected to measure the expression level of miR-30 family and CD90 by immunohistochemistry. The relationship between miR-30 family and CD90 protein expression was analyzed. Results The expression levels of miR-30c (P < 0.001), miR-30b (P=0.004), and miR-30e (P < 0.001) were significantly decreased in tumor tissues compared with adjacent tissues, and the expression level of CD90 in tumor tissues was significantly higher than that in adjacent normal tissues (P= 0.007). In addition, the expression levels of miR-30c (P=0.032) and miR-30e (P=0.015) were significantly high in negative staining for CD90 when compared with positive staining for CD90. Conclusion Taken together, we suggest that the miR-30 family may act as a tumor suppressor in HCC development and may modulate CD90 protein expression.
- hepatocellular carcinoma /
- miR-30 family /
- CD90 /
- cancer stem cell /
- EMT

HTML全文

图 1 CD90蛋白免疫组织化学结果(SP×400)

Figure 1. Expression level of CD90 protein in tissue microarray by immu⁃ nochemistry (SP×400)

下载: 全尺寸图片幻灯片

表 1 93例和121例肝细胞肝癌患者一般人口学特征和临床特征

Table 1. Baseline and clinical characteristics of 93 and 121 HCC patients

表 2 miR-30家族和CD90表达情况

Table 2. The expression of miR-30 family and CD90

表 3 CD90蛋白肝癌组织中表达与患者一般人口学和临床特征的关系

Table 3. The expression patterns of CD90 protein in tumor tissues stratified by baseline and clinical characteristics from 121 HCC patients

参考文献(26)

[1]	Kerr TA, Korenblat KM, Davidson NO. MicroRNAs and liver disease[J]. TranslRes, 2011, 157(4):241-252.
[2]	Fang Y, Xue JL, Shen Q, et al. MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/ Akt pathway in hepatocellular carcinoma[J]. Hepatology, 2012, 55 (6):1852-1862. doi: 10.1002/hep.25576
[3]	Wang J, Li J, Shen J, et al. MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma[J]. BMC Cancer, 2012, 12:227. doi: 10.1186/1471-2407-12-227
[4]	Bi Q, Tang S, Xia L, et al. Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF[J]. PLoS One, 2012, 7(6):e40169. doi: 10.1371/journal.pone.0040169
[5]	Zhang J, Yang Y, Yang T, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity[J]. Br JCancer, 2010, 103(8): 1215-1220. doi: 10.1038/sj.bjc.6605895
[6]	Su H, Yang JR, Xu T, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity[J]. Cancer Res, 2009, 69(3):1135-1142. doi: 10.1158/0008-5472.CAN-08-2886
[7]	Peng H, Luo J, Hao H, et al. MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B[J]. Oncol Rep, 2014, 31(5):2055-2062. doi: 10.3892/or.2014.3075
[8]	Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90. doi: 10.3322/caac.20107
[9]	Zhou P, Jiang W, Wu L, et al. miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma[J]. Dig Dis Sci, 2012, 57(5):1171-1180. doi: 10.1007/s10620-012-2099-2
[10]	Shao C, Yu Y, Yu L, et al. Amplification and up-regulation of microRNA-30b in oral squamous cell cancers[J]. Arch Oral Biol, 2012, 57(8):1012-1017. doi: 10.1016/j.archoralbio.2012.04.002
[11]	Jiang BY, Zhang XC, Su J, et al. BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification[J]. Mol Cancer, 2013, 12:61. doi: 10.1186/1476-4598-12-61
[12]	Jia W, Eneh JO, Ratnaparkhe S, et al. MicroRNA-30c-2* expressed in ovarian cancer cells suppresses growth factor-induced cellular proliferation and downregulates the oncogene BCL9[J]. Mol Cancer Res, 2011, 9(12):1732-1745. doi: 10.1158/1541-7786.MCR-11-0245
[13]	Yao J, Liang L, Huang S, et al. MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma[J]. Hepatology, 2010, 51(3):846-856. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=9ffcb4ce68c5b2c771521f1e3684d4bd
[14]	Wang W, Lin H, Zhou L, et al. MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is downregulated in hepatocellular carcinoma[J]. Eur J Surg Oncol, 2014, 40(11):1586-1594. doi: 10.1016/j.ejso.2013.11.008
[15]	Zhang J, Zhang H, Liu J, et al. miR-30 inhibits TGF-beta1-induced epithelial-to-mesenchymal transition in hepatocyte by targeting Snail1[J]. Biochem Biophys Res Commun, 2012, 417(3):1100-1105.
[16]	Guaita S, Puig I, Franci C, et al. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression[J]. J Biol Chem, 2002, 277(42): 39209-39216. doi: 10.1074/jbc.M206400200
[17]	Ouyang G, Wang Z, Fang X, et al. Molecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cells[J]. Cell Mol Life Sci, 2010, 67(15):2605-2618. doi: 10.1007/s00018-010-0338-2
[18]	Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell, 2008, 133 (4):704-715. doi: 10.1016/j.cell.2008.03.027
[19]	Rege TA, Hagood JS. Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis[J]. FASEB J, 2006, 20(8):1045-1054. doi: 10.1096/fj.05-5460rev
[20]	Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer[J]. Cancer Cell, 2008, 13(2):153-166. doi: 10.1016/j.ccr.2008.01.013
[21]	Sukowati CH, Anfuso B, Torre G, et al. The Expression of CD90/ Thy-1 in Hepatocellular Carcinoma: An In Vivo and In Vitro Study[J]. PLoS One, 2013, 8(10):e76830. doi: 10.1371/journal.pone.0076830
[22]	Bridge G, Monteiro R, Henderson S, et al. The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis[J]. Blood, 2012, 120(25):5063-5072. doi: 10.1182/blood-2012-04-423004
[23]	Dang H, Ding W, Emerson D, et al. Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics[J]. BMC Cancer, 2011, 11:396. doi: 10.1186/1471-2407-11-396
[24]	Pang RW, Poon RT. Cancer stem cell as a potential therapeutic target in hepatocellular carcinoma[J]. Curr Cancer Drug Targets, 2012, 12(9): 1081-1094.
[25]	DeSano JT, Xu L. MicroRNA regulation of cancer stem cells and therapeutic implications[J]. AAPS J, 2009, 11(4):682-692. doi: 10.1208/s12248-009-9147-7
[26]	Ji J, Wang XW. Clinical implications of cancer stem cell biology in hepatocellular carcinoma[J]. Semin Oncol, 2012, 39(4):461-472. doi: 10.1053/j.seminoncol.2012.05.011