Differentially expressed mRNA involved in the resistance of liver cancer to anlotinib

Junmou GU; Libo WANG; Dejun ZENG; Qinwei LU; Kai DONG; Ruopeng LIANG; Weijie WANG; Rongtao ZHU; Yuling SUN

doi:10.3969/j.issn.1001-5256.2021.02.022

Volume 37 Issue 2

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(2): 358-363

PDF( 3072 KB)

Differentially expressed mRNA involved in the resistance of liver cancer to anlotinib

DOI: 10.3969/j.issn.1001-5256.2021.02.022

1.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2.
Institute of Hepatobiliary and Pancreatic Diseases, Zhengzhou University, Zhengzhou 450052, China
3.
Zhengzhou Municipal Key Laboratory of Basic and Clinical Research on Hepatobiliary and Pancreatic Diseases, Zhengzhou 450052, China

Received Date: 2020-09-29
Accepted Date: 2020-11-27
Published Date: 2021-02-20

Abstract

Abstract

Objective To screen out the mRNAs involved in the resistance of hepatoma cells to anlotinib using ceRNA microarray. Methods High-dose shock combined with low-dose induction was used to culture hepatoma cells resistant to anlotinib, and CCK8 assay was used to verify the difference in the proliferation of drug-resistant hepatoma cells treated by anlotinib. The ceRNA microarray was used to screen out the differentially expressed genes between drug-resistant hepatoma cells and normal hepatoma cells, and real-time PCR was used to verify the differentially expressed genes detected by some microarrays. the independent samples t-test was used for comparison of continuous data between two groups, and the Kaplan-Meier method was used to analyze the overall survival of hepatoma cells samples, and the log-rank test was used to compare survival rates. Fisher's exact test was used for chip screening. Results There was a significant difference in gene expression between drug-resistant hepatoma cells and normal hepatoma cells, and 10 genes with the greatest difference were screened out for analysis by reducing the range. There were 4 genes associated with drug resistance and tumor growth, i.e., BIRC2, BIRC7, ABCC2, and MAPK8. There were significant reductions in the expression levels of BIRC2, ABCC2, and MAPK8 (P=0.001 4, 0.001 2, and 0.011 8), and there was a significant increase in the expression of BIRC7 (P < 0.001). The results of real-time PCR were consistent with those of microarray (t=10.74, 32.65, 18.34, and 2.80; P=0.000 4, 0.000 1, 0.000 1, and 0.044 8). The high expression of BIRC7 and the low expression of MAPK8 were associated with the significant reduction in survival time (P=0.022 0 and 0.005 6). Conclusion BIRC2, BIRC7, ABCC2, and MAPK8 are differentially expressed between anlotinib-resistant hepatoma cells and normal hepatoma cells and may be involved in the resistance of hepatoma cells to anlotinib.
- Liver Neoplasms,
- Anlotinib,
- Drug Resistance, Neoplasm,
- RNA, Messenger

FullText(HTML)

References(20)

References

[1]	Bureau of Medical Administration, National Health Commission of the People's Republic of China. Guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(2): 277-292. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.02.007 中华人民共和国国家卫生健康委员会医政医管局.原发性肝癌诊疗规范(2019年版)[J].临床肝胆病杂志, 2020, 36(2): 277-292. DOI: 10.3969/j.issn.1001-5256.2020.02.007
[2]	WANG S, WU QW, LI XK, et al. Interpretation of guidelines for diagnosis and treatment of primary liver cancer in China (2019 edition)[J]. J Clin Hepatol, 2020, 36(5): 996-999. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.05.009 王姗, 吴庆旺, 李小科, 等. 《原发性肝癌诊疗规范(2019年版)》解读[J].临床肝胆病杂志, 2020, 36(5): 996-999. DOI: 10.3969/j.issn.1001-5256.2020.05.009
[3]	SUN B, YANG XZ, XIE F, et al. Effect of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation on the survival of patients with hepatocellular carcinoma[J]. J Clin Hepatol, 2019, 35(1): 104-108. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2019.01.019 孙斌, 杨晓珍, 谢放, 等.索拉非尼联合经肝动脉化疗栓塞术和射频消融对肝细胞癌患者生存期的影响[J].临床肝胆病杂志, 2019, 35(1): 104-108. DOI: 10.3969/j.issn.1001-5256.2019.01.019
[4]	HE Z, YU Y, NONG Y, et al. Hepatitis B virus X protein promotes hepatocellular carcinoma invasion and metastasis via upregulating thioredoxin interacting protein[J]. Oncol Lett, 2017, 14(2): 1323-1332. DOI: 10.3892/ol.2017.6296
[5]	LIN B, SONG X, YANG D, et al. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRβ and FGFR1[J]. Gene, 2018, 654: 77-86. DOI: 10.1016/j.gene.2018.02.026
[6]	YE SL. Downstaging and conversion treatment of intermediate and advanced liver cancer should be taken seri-ously[J]. J Clin Hepatol, 2020, 36(2): 249-251. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.02.001 叶胜龙.重视中晚期肝癌的降期转化治疗[J].临床肝胆病杂志, 2020, 36(2): 249 -251. DOI: 10.3969/j.issn.1001-5256.2020.02.001
[7]	WANG YM, MENG Y, SHI XN, et al. Analysis of clinical efficacy, safety and prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer[J]. Chin J Hepatol, 2020, 28(7): 619-624. (in Chinese) DOI: 10.3760/cma.j.cn501113-20191020-00385 王亚梦, 孟宇, 师霄楠, 等.盐酸安罗替尼治疗晚期原发性肝癌的临床疗效、安全性及预后分析[J].中华肝脏病杂志, 2020, 28(7): 619-624. DOI: 10.3760/cma.j.cn501113-20191020-00385
[8]	PAN YF, FENG XL, YU X, et al. The clinical efficacy of transarterial chemoembolization combined with anlotinib in the treatment of advanced hepatocellular carcinoma[J]. Chin J Exp Surg, 2020, 37(3): 531-533. (in Chinese) DOI: 10.3760/cma.j.issn.1001-9030.2020.03.040 潘延凤, 冯晓丽, 余雪, 等.肝动脉化疗栓塞联合安罗替尼治疗晚期肝癌的临床研究[J].中华实验外科杂志, 2020, 37(3): 531-533. DOI: 10.3760/cma.j.issn.1001-9030.2020.03.040
[9]	YANG B, XIE H, WANG CP, et al. Study on Inhibition of arotinib on human intrahepatic cholangiocarcinoma cell line HCC-9810[J]. Chin J Med Guide, 2017, 19(12): 1389-1391. (in Chinese) DOI: 10.3969/j.issn.1009-0959.2017.12.037 杨斌, 谢辉, 王春平, 等.安罗替尼对人肝内胆管细胞癌细胞系HCC-9810作用研究[J].中国医药导刊, 2017, 19(12): 1389-1391. DOI: 10.3969/j.issn.1009-0959.2017.12.037
[10]	LIU K, YU Q, LI H, et al. BIRC7 promotes epithelial-mesenchymal transition and metastasis in papillary thyroid carcinoma through restraining autophagy[J]. Am J Cancer Res, 2020, 10(1): 78-94.
[11]	DOU H, BUETOW L, SIBBET GJ, et al. BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer[J]. Nat Struct Mol Biol, 2012, 19(9): 876-883. DOI: 10.1038/nsmb.2379
[12]	SAMANTA D, HUANG TY, SHAH R, et al. BIRC2 expression impairs anti-cancer immunity and immunotherapy efficacy[J]. Cell Rep, 2020, 32(8): 108073. DOI: 10.1016/j.celrep.2020.108073
[13]	GYRD-HANSEN M, MEIER P. IAPs: From caspase inhibitors to modulators of NF-kappaB, inflammation and cancer[J]. Nat Rev Cancer, 2010, 10(8): 561-574. DOI: 10.1038/nrc2889
[14]	MA O, CAI WW, ZENDER L, et al. MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression[J]. Cancer Res, 2009, 69(6): 2559-2567. DOI: 10.1158/0008-5472.CAN-08-2929
[15]	CAMPBELL GR, BRUCKMAN RS, CHU YL, et al. SMAC mimetics induce autophagy-dependent apoptosis of HIV-1-infected resting memory CD4⁺ T cells[J]. Cell Host Microbe, 2018, 24(5): 689-702. DOI: 10.1016/j.chom.2018.09.007
[16]	CORPECHOT C, BARBU V, CHAZOUILLÈRES O, et al. Genetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders[J]. Liver Int, 2020, 40(1): 163-174. DOI: 10.1111/liv.14260
[17]	RAZALI RH, NOORIZHAB M, JAMARI H, et al. Association of ABCC2 with levels and toxicity of methotrexate in malaysian childhood acute lymphoblastic leukemia (ALL)[J]. Pediatr Hematol Oncol, 2020, 37(3): 185-197. DOI: 10.1080/08880018.2019.1705949
[18]	WU L, LI Y, SONG Y, et al. A recurrent ABCC2 p.G693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China[J]. Orphanet J Rare Dis, 2020, 15(1): 74. DOI: 10.1186/s13023-020-1346-4
[19]	NGAN HL, LIU Y, FONG AY, et al. MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling[J]. Life Sci Alliance, 2020, 3(6): e201900545. DOI: 10.26508/lsa.201900545
[20]	XU P, ZHANG G, HOU S, et al. MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway[J]. Biomed Pharmacother, 2018, 106: 1419-1427. DOI: 10.1016/j.biopha.2018.06.084

Relative Articles

Supplements(0)

Cited By

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(6)

Get Citation

PDF

XML

Article Metrics

Article views (580) PDF downloads(28)

Differentially expressed mRNA involved in the resistance of liver cancer to anlotinib

DOI: 10.3969/j.issn.1001-5256.2021.02.022

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Differentially expressed mRNA involved in the resistance of liver cancer to anlotinib

DOI: 10.3969/j.issn.1001-5256.2021.02.022

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content