Advances of the mechanism and application of microRNAs in hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-1221.2020.01.010

Abstract

Abstract:

MicroRNAs (miRNAs) represent a class of small-sized endogenous non-coding RNA involved in most biological processes by imposing regulation on the expression of target genes. In recent years, the understanding as to the mechanisms of miRNAs in the hepatocellular carcinoma (HCC) have been improved on a continued basis. As a significant regulator and major participant in the process, miRNAs have been regarded as a crucial target in early diagnosis, target treatment and the prognosis evaluation of HCC. In this paper, our emphasis is placed on the role that miRNAs play in the developmental process, the multi-drug resistance of HCC and the value of miRNAs as the potential therapeutic target for HCC, and a summary is made of the progress made in research conducted into the function, molecular pathways and application of miRNAs in HCC.

Key words: MicroRNAs, Hepatocellular carcinoma, Signal pathway, Multidrug resistance, Diagnosis and treatment

Xiaokun Ma, Wei Xia. Advances of the mechanism and application of microRNAs in hepatocellular carcinoma[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(01): 52-56.

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通路	名称	抑癌/致癌	作用	参考文献
mTOR通路	miR-223	抑癌	miR-223过表达时抑制Ras相关蛋白Rab1而导致mTOR通路失活	[21]
	miR-142	抑癌	miR-142是一种抑癌基因，它的超甲基化可导致自身功能丧失，从而促进HCC细胞中转化生长因子-β介导的肿瘤生长和转移	[22]
	miR-199b-5p	抑癌	miR-199b-5p可抑制转化生长因子-β诱导的上皮细胞-间充质转化相关性状，并直接靶向HCC中的N-钙粘蛋白而发挥抑癌基因功能	[23]
	miR-497，miR-99a	抑癌	miR-497和miR-99a通过抑制IGF1R/mTOR信号通路发挥抑癌基因功能	[24]
	miR-296-5p	抑癌	miR-296-5p的低表达与HCC生长中mTOR通路的激活直接相关，其通过靶向AKT2在体外抑制HCC细胞的增殖、迁移和侵袭	[25]
	miR-15b-5p	抑癌	miR-15b-5p可抑制Opa相互作用蛋白5介导的HCC致癌信号而发挥抑癌基因功能	[26]
	miR-29c-3p	抑癌	miR-29c-3p可通过靶向DNMT3B和LATS1相关的Hippo信号在HCC中发挥相应的抑癌作用	[15]
Wnt通路	miR-320a	抑癌	β-连环蛋白的磷酸化、调节和降解是Wnt通路的本质。miR-320a通过靶向HCC通路中的β-连环蛋白而充当HCC的抑癌基因	[27]
	miR-18a	致癌	通过抑制转录因子KLF4来负向调节β连环蛋白的表达，进而促使HCC细胞系的增殖和迁移	[28]
	miR-552	致癌	通过阻断Wnt抑制因子1介导的糖原合成激酶-3β去磷酸化促进HCC的发生和发展	[14]
JAK/STAT通路	miR-214-3p	抑癌	PIM-1是一种编码丝氨酸/苏氨酸激酶蛋白的癌基因，其转录是由STAT蛋白启动。T3诱导miR-214-3p表达并通过PIM-1抑制细胞增殖，有助于抑制HCC肿瘤细胞的形成	[29]
JAK/STAT通路	miR-30e，miR-340	抑癌	JAK-1是其直接靶点，miR-30e及miR-340通过调节JAK1/STAT3信号通路抑制HCC细胞的增殖、迁移和侵袭	[30,31]
MAPK通路	miR-346	抑癌	SMYD3是HCC中表达上调的癌基因。SMYD3增加MAP激酶信号通路，可促进Ras驱动癌的形成，导致MAP3K2的甲基化。通过抑制SMYD3的表达来恢复miR-346的表达水平，能够阻止HCC细胞进一步增殖	[32]

通路	名称	抑癌/致癌	作用	参考文献
mTOR通路	miR-223	抑癌	miR-223过表达时抑制Ras相关蛋白Rab1而导致mTOR通路失活	[21]
	miR-142	抑癌	miR-142是一种抑癌基因，它的超甲基化可导致自身功能丧失，从而促进HCC细胞中转化生长因子-β介导的肿瘤生长和转移	[22]
	miR-199b-5p	抑癌	miR-199b-5p可抑制转化生长因子-β诱导的上皮细胞-间充质转化相关性状，并直接靶向HCC中的N-钙粘蛋白而发挥抑癌基因功能	[23]
	miR-497，miR-99a	抑癌	miR-497和miR-99a通过抑制IGF1R/mTOR信号通路发挥抑癌基因功能	[24]
	miR-296-5p	抑癌	miR-296-5p的低表达与HCC生长中mTOR通路的激活直接相关，其通过靶向AKT2在体外抑制HCC细胞的增殖、迁移和侵袭	[25]
	miR-15b-5p	抑癌	miR-15b-5p可抑制Opa相互作用蛋白5介导的HCC致癌信号而发挥抑癌基因功能	[26]
	miR-29c-3p	抑癌	miR-29c-3p可通过靶向DNMT3B和LATS1相关的Hippo信号在HCC中发挥相应的抑癌作用	[15]
Wnt通路	miR-320a	抑癌	β-连环蛋白的磷酸化、调节和降解是Wnt通路的本质。miR-320a通过靶向HCC通路中的β-连环蛋白而充当HCC的抑癌基因	[27]
	miR-18a	致癌	通过抑制转录因子KLF4来负向调节β连环蛋白的表达，进而促使HCC细胞系的增殖和迁移	[28]
	miR-552	致癌	通过阻断Wnt抑制因子1介导的糖原合成激酶-3β去磷酸化促进HCC的发生和发展	[14]
JAK/STAT通路	miR-214-3p	抑癌	PIM-1是一种编码丝氨酸/苏氨酸激酶蛋白的癌基因，其转录是由STAT蛋白启动。T3诱导miR-214-3p表达并通过PIM-1抑制细胞增殖，有助于抑制HCC肿瘤细胞的形成	[29]
JAK/STAT通路	miR-30e，miR-340	抑癌	JAK-1是其直接靶点，miR-30e及miR-340通过调节JAK1/STAT3信号通路抑制HCC细胞的增殖、迁移和侵袭	[30,31]
MAPK通路	miR-346	抑癌	SMYD3是HCC中表达上调的癌基因。SMYD3增加MAP激酶信号通路，可促进Ras驱动癌的形成，导致MAP3K2的甲基化。通过抑制SMYD3的表达来恢复miR-346的表达水平，能够阻止HCC细胞进一步增殖	[32]

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