Role of differential expression and regulatory mechanism of miR-152-3p target proteins in the recurrence of hepatocellular carcinoma

Chenxia LIU; Kai CHANG; Wanlin NA; Yanyan WANG; Dong MOU; Hua LI; Zhongyong JIANG; Yuan LIU; Jie XIONG

doi:10.3969/j.issn.1001-5256.2021.02.023

Volume 37 Issue 2

Mar. 2021

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(2): 364-369

PDF( 4086 KB)

Role of differential expression and regulatory mechanism of miR-152-3p target proteins in the recurrence of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.02.023

Chenxia LIU^{1, 2a},
Kai CHANG^2a,
Wanlin NA^2a,
Yanyan WANG^2a,
Dong MOU^2b,
Hua LI^2c,
Zhongyong JIANG^2a,
Yuan LIU^2a,
Jie XIONG^{1, 2a
,
,}

1.
School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
2a.
Department of Clinical Laboratory, The General Hospital of Western Theater Command, Chengdu 610083, China
2b.
Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu 610083, China
2c.
Department of Oncology, The General Hospital of Western Theater Command, Chengdu 610083, China

Received Date: 2020-09-04
Accepted Date: 2020-10-19
Published Date: 2021-02-20

Abstract

Abstract

Objective To investigate the difference in protein expression between hepatocellular carcinoma (HCC) patients with recurrence and those with good prognosis, the differential expression and regulatory mechanism of miR-152-3p target proteins, and the role of miR-152-3p in the recurrence of HCC. Methods TMT-labeled proteomic sequencing and RT-PCR were used to measure the expression of proteins and the expression of miR-152-3p in the HCC tissue of six patients with recurrence at 2 years after HCC resection and six patients with good prognosis at 5 years. Six databases were used to analyze the target genes of miR-152-3p, and Gene Ontology, DAVID, and REACTOME databases were used to perform target gene screening, enrichment annotation, and signal transduction pathway enrichment analysis. Gene mutation frequency and survival curve analysis were performed for the target genes of miR-152-3p to verify the role of miR-152-3p target genes in patients with HCC recurrence. The independent samples t-test was used for comparison of continuous data between two groups, and a Kaplan-Meier analysis was performed to investigate the survival rates of liver-related genes. Results Compared with the patients with HCC recurrence, the patients with good prognosis after HCC resection had a significantly higher transcriptional expression level of miR-152-3p in HCC tissue (P < 0.05). The results of protein sequencing showed that there were 365 differentially expressed proteins in HCC tissue between the patients with good prognosis and the patients with recurrence, and the analysis of HCC recurrence databases showed that 17 proteins were regulated by miR-152-3p. Further analysis of the signaling pathways showed that the function of the 17 target genes regulated by miR-152-3p was enriched in the translation and regulation of mitochondria and ribosome, and multiple enrichment revealed that six target genes were closely associated with mitochondrial respiratory chain complex, i.e., AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1. Gene mutation frequency and survival curve analysis showed that the loss or weakening of the function of mitochondrial respiratory chain-related target proteins seriously affected the prognosis and survival rate of patients. Conclusion There is a significant difference in the expression of miR-152-3p in HCC tissue between patients with good prognosis and those with recurrence after HCC resection, and miR-152-3p may lead to the recurrence of HCC by regulating the target genes AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1, acting on the mitochondrial respiratory chain, and affecting the oxidative respiratory function of cells.
- Carcinoma, Hepatocellular,
- miR-152-3p,
- Recurrence

FullText(HTML)

References(20)

References

[1]	DUTTA R, MAHATO RI. Recent advances in hepatocellular carcinoma therapy[J]. Pharmacol Ther, 2017, 173(5): 106-117.
[2]	ZHANG Z, MA L, GOSWAMI S, et al. Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma[J]. OncoImmunology, 2019, 8(4): 1-11.
[3]	ZHAO ZJ, HU Y, SHEN XH, et al. HBx represses RIZ1 expression by DNA methyltransferase 1 involvement in decreased miR-152 in hepatocellular carcinoma[J]. Oncol Rep, 2017, 37(5): 2811. DOI: 10.3892/or.2017.5518
[4]	DUAN YF, ZHAO QX, JING X. Effect of long non-coding RNAs on glycolytic pathway in primary liver cancer and related mechanisms[J]. J Clin Hepatol, 2019, 35(6): 1374-1376. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2019.06.043 段艺菲, 赵清喜, 荆雪.长链非编码RNA对原发性肝癌中糖酵解途径的影响机制[J].临床肝胆病杂志, 2019, 35(6): 1374-1376. DOI: 10.3969/j.issn.1001-5256.2019.06.043
[5]	DING J, DUAN BW, DI L. Expression and mechanism of microRNA and Na+/H+ exchanger regulatory factor 1 on hepatocellular carcinoma[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 59-64.(in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003015.htm 丁兢, 段斌炜, 邸亮.微小RNA-320a和钠氢交换调控因子1在肝细胞癌中的表达及机制[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 59-64. https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003015.htm
[6]	QU ZN, LIN L, ZHONG W, et al. Meta-analysis of value of circulating microRNA 122 on diagnosis of hepatocellular carcinoma[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 23-28.(in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003007.htm 屈振南, 林霖, 钟伟, 等.循环微小RNA-122诊断肝细胞癌的Meta分析[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 23-28. https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003007.htm
[7]	ZHOU JJ, ZHANG YJ, QI YH, et al. MicroRNA-152 inhibits tumor cell growth by directly targeting RTKN in hepatocellular carcinoma[J]. Oncol Rep, 2017, 37(2): 1227. DOI: 10.3892/or.2016.5290
[8]	MIQUELESTORENA-STANDLEY E, TALLET A, COLLIN C, et al. Interest of variations in microRNA-152 and-122 in a series of hepatocellular carcinomas related to hepatitis C virus infection[J]. Hepatol Res, 2018, 48(7): 566-573. DOI: 10.1111/hepr.12915
[9]	BILIC′ P, GUILLEMIN N, KOVACˇEVIC′ A, et al. Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach[J]. J Proteomics, 2018, 179: 110-121. DOI: 10.1016/j.jprot.2018.03.007
[10]	CHANG K, JIANG ZY, REN JL, et al. Bioinformatics prediction of miR-130b-3p target genes associated with diabetic nephropathy[J]. J Chongqing Med Univ, 2018, 43(6): 788-792. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201806011.htm 常凯, 江忠勇, 任俊龙, 等.糖尿病肾病相关miR-130b-3p靶点的生物信息学预测[J].重庆医科大学学报, 2018, 43(6): 788-792. https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201806011.htm
[11]	CHEN L, ZHANG YH, WANG SP, et al. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways[J]. PLoS One, 2017, 12(9): e0184129. DOI: 10.1371/journal.pone.0184129
[12]	WANG F, YING H, HE B, et al. Circulating miR-148/152 family as potential biomarkers in hepatocellular carcinoma[J]. Tumour Biol, 2016, 37(4): 4945-4953. DOI: 10.1007/s13277-015-4340-z
[13]	HUANG J, WANG Y, GUO Y, et al. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1[J]. Hepatology, 2010, 52(1): 60-70. DOI: 10.1002/hep.23660
[14]	DANG YW, ZENG J, HE RQ, et al. Effects of miR-152 on cell growth inhibition, motility suppression and apoptosis induction in hepatocellular carcinoma cells[J]. Asian Pac J Cancer Prev, 2014, 15(12): 4969-4976. DOI: 10.7314/APJCP.2014.15.12.4969
[15]	IRYNA K, VOLODYMYR T, ALINE DC, et al. MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis[J]. Oncotarget, 2016, 7(2): 1276-1287. DOI: 10.18632/oncotarget.6004
[16]	FORMOSA LE, MASAKAZU M, FRAZIER AE, et al. Characterization of mitochondrial FOXRED1 in the assembly of respiratory chain complex I[J]. Hum Mol Genet, 2015, 24(10): 2952-2965. DOI: 10.1093/hmg/ddv058
[17]	DAGDA RK, GUSDON AM, PIEN I, et al. Mitochondrially localized PKA reverses mitochondrial pathology and dysfunction in a cellular model of Parkinson's disease[J]. Cell Death Differ, 2011, 18(12): 1914-1923. DOI: 10.1038/cdd.2011.74
[18]	YU J, ZHANG Y, ZHOU DX, et al. Higher expression of A-kinase anchoring-protein 1 predicts poor prognosis in human hepatocellular carcinoma[J]. Oncol Lett, 2018, 16(1): 131-136.
[19]	JIANG ZJ, CHEN J, LI LQ. Research progress of long non-coding RNA in the invasion and metastasis of hepatocellular carcinoma[J]. J Med Postgraduates, 2019, 32(7): 765-770. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-JLYB201907020.htm 蒋志俊, 陈洁, 黎乐群.长链非编码RNA在肝癌侵袭转移中的研究进展[J].医学研究生学报, 2019, 32(7): 765-770. https://www.cnki.com.cn/Article/CJFDTOTAL-JLYB201907020.htm
[20]	ZHANG XC, LI B. Towards understanding the mechanisms of proton pumps in Complex-Ⅰ of the respiratory chain[J]. Biophy Rep, 2019, 5(5-6): 219-234. DOI: 10.1007/s41048-019-00094-7

Relative Articles

Supplements(0)

Cited By

Cited by

Periodical cited type(7)

1.	杜鑫，高白银，黎倩. 耐高压静脉套管针对乳腺癌患者化疗后MRI检查中对比剂渗漏的影响. 癌症进展. 2022(04): 419-422 .
2.	陈诚，王俊杰，吴涯昆. 小儿巨大肝脏局灶性结节性增生1例报告. 临床肝胆病杂志. 2022(06): 1370-1372 . 本站查看
3.	赖婳妤，肖艳红，温勇峰. 磁共振特异对比剂莫迪司在肝癌和局灶结节性增生鉴别诊断中的应用价值分析. 影像研究与医学应用. 2020(07): 143-144 .
4.	滕高钦，马金良，张传海，蒋勇，周虹. 肝腺瘤分型回顾学习附1例病例报告. 齐齐哈尔医学院学报. 2020(21): 2701-2704 .
5.	高维克，戴朝六. 肝腺瘤的临床特点、诊断及治疗(附11例报告). 山东医药. 2018(07): 70-72 .
6.	张媛媛. 耐高压静脉套管针在防止高压注射器磁共振增强扫描时造影剂外渗的护理效果. 实用医学影像杂志. 2018(05): 455-457 .
7.	任洪伟，安维民，董景辉，刘长春，叶慧义. 扩散加权成像对肝脏常见含脂质肿瘤的鉴别诊断. 中国医学影像学杂志. 2017(06): 457-460+464 .

Other cited types(2)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(4) / Tables(5)

Get Citation

PDF

XML

Article Metrics

Article views (612) PDF downloads(29)

Role of differential expression and regulatory mechanism of miR-152-3p target proteins in the recurrence of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.02.023