CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma

Yu,Qianle; Gao,Kai

doi:10.3892/mmr.2020.11336

CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma

Authors:
- Qianle Yu
- Kai Gao
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Affiliations: Department of General Surgery and Institute of Digestive Surgery, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan 410006, P.R. China, Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: July 13, 2020 https://doi.org/10.3892/mmr.2020.11336
Pages: 2245-2252
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) remains the most common malignant cancer worldwide. Numerous studies have indicated that C‑type lectin domain family 4 member M (CLEC4M) is associated with tumor progression; however, the biological functions of CLEC4M in HCC have not been investigated. In the present study, CLEC4M overexpression was observed to be associated with a favorable patient overall, relapse‑free, progression‑free and disease‑specific survival by using the KMplot™ database. The present study then concentrated specifically on the functions of CLEC4M by performing cell counting kit‑8 proliferation, 5‑Ethynyl‑2'‑deoxyuridine and flow cytometric assays. CLEC4M overexpression inhibited proliferation and enhanced apoptosis in Huh7 and PLC/PRF/5 cells. Furthermore, the results demonstrated by using western blotting that CLEC4M overexpression inhibited the Janus kinase 1/signal transducer and activator of transcription 3 pathway, which is involved in various types of tumors including HCC. In conclusion, the present study reported that CLEC4M may be considered as a novel indicator of HCC and may provide a theoretical basis for improving the survival of patients with HCC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2004. View Article : Google Scholar
3	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
4	Bruix J and Llovet JM: Major achievements in hepatocellular carcinoma. Lancet. 373:614–616. 2009. View Article : Google Scholar : PubMed/NCBI
5	Chen C and Wang G: Mechanisms of hepatocellular carcinoma and challenges and opportunities for molecular targeted therapy. World J Hepatol. 7:1964–1970. 2015. View Article : Google Scholar : PubMed/NCBI
6	Zhang F, Ren S and Zuo Y: DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection. Int Rev Immunol. 33:54–66. 2014. View Article : Google Scholar : PubMed/NCBI
7	Jiang Y, Zhang C, Chen K, Chen Z, Sun Z, Zhang Z, Ding D, Ren S and Zuo Y: The clinical significance of DC-SIGN and DC-SIGNR, which are novel markers expressed in human colon cancer. PLoS One. 9:e1147482014. View Article : Google Scholar : PubMed/NCBI
8	Na H, Liu X, Li X, Zhang X, Wang Y, Wang Z, Yuan M, Zhang Y, Ren S and Zuo Y: Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis. J Hematol Oncol. 10:282017. View Article : Google Scholar : PubMed/NCBI
9	Zhang Y, Zhang Q, Zhang M, Yuan M, Wang Z, Zhang J, Zhou X, Zhang Y, Lin F, Na H, et al: DC-SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis. Mol Cancer. 16:782017. View Article : Google Scholar : PubMed/NCBI
10	Liu X, Zhang H, Su L, Yang P, Xin Z, Zou J, Ren S and Zuo Y: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells. Mol Cell Biochem. 407:151–160. 2015. View Article : Google Scholar : PubMed/NCBI
11	Liao J, Xu T, Zheng JX, Lin JM, Cai QY, Yu DB and Peng J: Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway. Int J Mol Med. 32:79–84. 2013. View Article : Google Scholar : PubMed/NCBI
12	Mao J, Hu X, Pang P, Zhou B, Li D and Shan H: miR-30e acts as a tumor suppressor in hepatocellular carcinoma partly via JAK1/STAT3 pathway. Oncol Rep. 38:393–401. 2017. View Article : Google Scholar : PubMed/NCBI
13	Cao L, Cheng H, Jiang Q, Li H and Wu Z: APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma. Aging. 12:4573–4591. 2020. View Article : Google Scholar : PubMed/NCBI
14	Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, Thorgeirsson SS, Sun Z, Tang ZY, Qin LX and Wang XW: A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 70:10202–10212. 2010. View Article : Google Scholar : PubMed/NCBI
15	Mas VR, Maluf DG, Archer KJ, Yanek K, Kong X, Kulik L, Freise CE, Olthoff KM, Ghobrial RM, McIver P and Fisher R: Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med. 15:85–94. 2009. View Article : Google Scholar : PubMed/NCBI
16	Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, Schwartz M, Fiel I, Thung S, Mazzaferro V, Bruix J, et al: Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 45:938–947. 2007. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Zhang Q, Zhang M, Yuan M, Wang Z, Zhang J, Zhou X, Zhang Y, Lin F, Na H, et al: DC-SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis. Mol Cancer. 16:782017. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Tan LM, Li X, Qiu CF, Zhu T, Hu CP, Yin JY, Zhang W, Zhou HH and Liu ZQ: CLEC4M is associated with poor prognosis and promotes cisplatin resistance in NSCLC patients. J Cancer. 10:6374–6383. 2019. View Article : Google Scholar : PubMed/NCBI
20	Wen W, Liang W, Wu J, Kowolik CM, Buettner R, Scuto A, Hsieh MY, Hong H, Brown CE, Forman SJ, et al: Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer. Mol Cancer Ther. 13:3037–3048. 2014. View Article : Google Scholar : PubMed/NCBI
21	Yan CM, Zhao YL, Cai HY, Miao GY and Ma W: Blockage of PTPRJ promotes cell growth and resistance to 5-FU through activation of JAK1/STAT3 in the cervical carcinoma cell line C33A. Oncol Rep. 33:1737–1744. 2015. View Article : Google Scholar : PubMed/NCBI
22	Xia HB, Wang HJ, Song SS, Zhang JG, He XL, Hu ZM, Zhang CW, Huang DS and Mou XZ: Decreased DC-SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis. Oncol Lett. 19:69–76. 2020.PubMed/NCBI
23	Zhang Z, Chen K, Yan L, Yang Z, Zhu Z, Chen C, Zeng J, Wei W, Qi X, Ren S and Zuo Y: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in non-Hodgkin lymphoma and significant correlations with lactic acid dehydrogenase and β2-microglobulin. Biochem Cell Biol. 91:214–220. 2013. View Article : Google Scholar : PubMed/NCBI
24	Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, Ramos AH, Saksena G, Baca SC, Baselga J, et al: Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res. 72:4383–4393. 2012. View Article : Google Scholar : PubMed/NCBI
25	Cao W, Liu Y, Zhang R, Zhang B, Wang T, Zhu X, Mei L, Chen H, Zhang H, Ming P and Huang L: Homoharringtonine induces apoptosis and inhibits STAT3 via IL-6/JAK1/STAT3 signal pathway in Gefitinib-resistant lung cancer cells. Sci Rep. 5:84772015. View Article : Google Scholar : PubMed/NCBI
26	Tactacan CM, Phua YW, Liu L, Zhang L, Humphrey ES, Cowley M, Pinese M, Biankin AV and Daly RJ: The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling. Mol Cancer. 14:1392015. View Article : Google Scholar : PubMed/NCBI
27	van der Zee M, Sacchetti A, Cansoy M, Joosten R, Teeuwssen M, Heijmans-Antonissen C, Ewing-Graham PC, Burger CW, Blok LJ and Fodde R: IL6/JAK1/STAT3 signaling blockade in endometrial cancer affects the ALDHhi/CD126+ Stem-like component and reduces tumor burden. Cancer Res. 75:3608–3622. 2015. View Article : Google Scholar : PubMed/NCBI