Nan YANG, Tianxiang CHEN, Runkun LIU, et al. Enhanced expression of interferon-induced protein with tetratricopeptide repeats 5 promotes migration and invasion of hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2020, 42(21): 2093-2099.
DOI:
Nan YANG, Tianxiang CHEN, Runkun LIU, et al. Enhanced expression of interferon-induced protein with tetratricopeptide repeats 5 promotes migration and invasion of hepatocellular carcinoma cells[J]. Journal of Third Military Medical University, 2020, 42(21): 2093-2099. DOI: 10.16016/j.1000-5404.202005290.
Enhanced expression of interferon-induced protein with tetratricopeptide repeats 5 promotes migration and invasion of hepatocellular carcinoma cells
clinical significance and possible underlying mechanism of interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) in human hepatocellular carcinoma (HCC).
Methods
2
Liver tumor tissues and adjacent normal tissues were harvested from 97 HCC patients diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University between Jan Uary
2013 and December
2013. Real-time quantitative PCR
Western blotting and immunohistochemical assay were used to detect the IFIT5 expression level in 97 pairs of HCC tissue and para-cancerous tissues. The relationships of the expression level of IFIT5 with clinical pathological indexes and survival rate were analyzed. Its protein expression was also detected with Western blotting in various HCC cell lines and normal liver cell line. After the overexpression plasmid of IFIT5 was transfected into the HCC cell line Hep3B (low IFIT5 expression)
and IFIT5 siRNA was induced into the HCCLM3 cells (high IFIT5 expression)
Transwell assay was performed to measure the effects of IFIT5 on the invasion and migration abilities of above the 2 kinds of HCC cells. The expression levels of EMT-related proteins were determined by Western blotting.
Results
2
The expression level of IFIT5 was significantly higher in HCC tissues than the adjacent normal tissues (
P
<
0.05)
and its high level was significantly associated with TNM stage (
P
=0.018) and vascular infiltration (
P
=0.009). The patients with higher IFIT5 level had a worse 5-year survival rate than those with lower level (
P
<
0.05). Overexpression of IFIT5 significantly promoted the invasion and migration of HCC cells (
P
<
0.05) and the EMT of HCC cells (
P
<
0.05).
Conclusion
2
IFIT5 is up-regulated in HCC tissues
and its high expression is correlated with the malignant pathological features. IFIT5 can promote the invasion and migration of HCC cells by regulating EMT.
关键词
Keywords
references
SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70 (1): 7-30. DOI: 10.3322/caac.21590.
EL-SERAG H B, RUDOLPH K L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis[J]. Gastroenterology, 2007, 132(7): 2557-2576. DOI:10.1053/j.gastro.2007.04.061.
JAFRI W, KAMRAN M. Hepatocellular carcinoma in Asia: a challenging situation[J]. Euroasian J Hepatogastroenterol, 2019, 9(1): 27-33. DOI:10.5005/jp-journals-10018-1292.
KATIBAH G E, QIN Y D, SIDOTE D J, et al . Broad and adaptable RNA structure recognition by the human interferon-induced tetratricopeptide repeat protein IFIT5[J ] . Proc Natl Acad Sci USA, 2014, 111(33): 12025-12030. DOI:10.1073/pnas.1412842111.
KATIBAH G E, LEE H J, HUIZAR J P, et al . tRNA binding, structure, and localization of the human interferon-induced protein IFIT5[J ] . Mol Cell, 2013, 49(4): 743-750. DOI:10.1016/j.molcel.2012.12.015.
ROHAIM M A, SANTHAKUMAR D, NAGGAR R F E, et al . Chickens expressing IFIT5 ameliorate clinical outcome and pathology of highly pathogenic avian influenza and velogenic Newcastle disease viruses[J ] . Front Immunol, 2018, 9: 2025. DOI:10.3389/fimmu.2018.02025.
HUANG J, LO U G, WU S Q, et al . The roles and mechanism of IFIT5 in bladder cancer epithelial-mesenchymal transition and progression[J ] . Cell Death Dis, 2019, 10(6): 437. DOI:10.1038/s41419-019-1669-z.
LO U G, BAO J M, CEN J J, et al . Interferon-induced IFIT5 promotes epithelial-to-mesenchymal transition leading to renal cancer invasion[J ] . Am J Clin Exp Urol, 2019, 7(1): 31-45.
LO U G, PONG R C, YANG D E, et al . IFNγ-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via miRNA processing[J ] . Cancer Res, 2019, 79(6): 1098-1112. DOI:10.1158/0008-5472.CAN-18-2207.
FAIVRE S, RIMASSA L, FINN R S. Molecular therapies for HCC: Looking outside the box[J]. J Hepatol, 2020, 72(2): 342-352. DOI:10.1016/j.jhep.2019.09.010.
LIU Z K, WANG Y F, DOU C W, et al . Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma[J ] . Theranostics, 2018, 8(17): 4649-4663. DOI:10.7150/thno.26789.
PIDUGU V K, PIDUGU H B, WU M M, et al . Emerging functions of human IFIT proteins in cancer[J ] . Front Mol Biosci, 2019, 6: 148. DOI:10.3389/fmolb.2019.00148.
ZHANG B H, LIU X Y, CHEN W, et al . IFIT5 potentiates anti-viral response through enhancing innate immune signaling pathways[J ] . Acta Biochim Biophys Sin (Shanghai), 2013, 45(10): 867-874. DOI:10.1093/abbs/gmt088.
MIEDZIAK B, DOBIEŻYŃSKA A, DARZ·YNKIEWICZ Z M, et al . Kinetic analysis of IFIT1 and IFIT5 interactions with different native and engineered RNAs and its consequences for designing mRNA-based therapeutics[J ] . RNA, 2020, 26(1): 58-68. DOI:10.1261/rna.073304.119.
ZHENG C S, ZHENG Z H, ZHANG Z F, et al . IFIT5 positively regulates NF-κB signaling through synergizing the recruitment of IκB kinase (IKK) to TGF-β-activated kinase 1 (TAK1)[J ] . Cell Signal, 2015, 27(12): 2343-2354. DOI:10.1016/j.cellsig.2015.08.018.
GIANNELLI G, KOUDELKOVA P, DITURI F, et al . Role of epithelial to mesenchymal transition in hepatocellular carcinoma[J ] . J Hepatol, 2016, 65(4): 798-808. DOI:10.1016/j.jhep.2016.05.007.
SCHEAU C, BADARAU I A, COSTACHE R, et al . The role of matrix metalloproteinases in the epithelial-mesenchymal transition of hepatocellular carcinoma[J ] . Anal Cell Pathol (Amst), 2019, 2019: 9423907. DOI:10.1155/2019/9423907.
GURZU S, KOBORI L, FODOR D, et al . Epithelial mesenchymal and endothelial mesenchymal transitions in hepatocellular carcinoma: a review[J ] . Biomed Res Int, 2019, 2019: 2962580. DOI:10.1155/2019/2962580.
MIR N, JAYACHANDRAN A, DHUNGEL B, et al . Epithelial-to-mesenchymal transition: a mediator of sorafenib resistance in advanced hepatocellular carcinoma[J ] . Curr Cancer Drug Targets, 2017, 17(8): 698-706. DOI:10.2174/1568009617666170427104356.