Open Access

CHD1L is associated with poor survival and promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma

  • Authors:
    • Shimiao Li
    • Yi Chai
    • Yanbao Ding
    • Tinghao Yuan
    • Changwen Wu
    • Changwen Huang
  • View Affiliations

  • Published online on: May 28, 2019     https://doi.org/10.3892/or.2019.7174
  • Pages: 657-669
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Chromodomain helicase/ATPase DNA‑binding protein 1‑like gene (CHD1L) is a new oncogene which has been confirmed to be crucial to the progression of many solid tumors. In the present study, the expression of CHD1L was found to be upregulated in intrahepatic cholangiocarcinoma (ICC), which was significantly associated with histological differentiation (P=0.011), vascular invasion (P=0.002), lymph node metastasis (P=0.008) and TNM stage (P=0.001). Kaplan‑Meier survival analysis revealed that ICC patients with positive CHD1L expression had shorter overall and disease‑free survival than those with negative CHD1L expression. Functional study found that CHD1L exhibited strong oncogenic roles, including increased cell growth by CCK‑8 assay, colony formation by plate colony formation assay, G1/S transition by flow cytometry and tumor formation in nude mice. In addition, RNAi‑mediated silencing of CHD1L inhibited ICC invasion and metastasis by wound healing, Transwell migration and Matrigel invasion assays in vitro and in vivo. Collectively, our results show that CHD1L is upregulated and promotes the proliferation and metastasis of ICC cells. CHD1L acts as an oncogene and may be a prognostic factor or therapeutic target for patients with ICC.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Wang Y, Li J, Xia Y, Gong R, Wang K, Yan Z, Wan X, Liu G, Wu D, Shi L, et al: Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 31:1188–1195. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Haga H and Patel T: Molecular diagnosis of intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 22:114–123. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM and Gores GJ: Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 60:1268–1289. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Okumura S, Kaido T, Hamaguchi Y, Kobayashi A, Shirai H, Fujimoto Y, Iida T, Yagi S, Taura K, Hatano E, et al: Impact of skeletal muscle mass, muscle quality, and visceral adiposity on outcomes following resection of intrahepatic cholangiocarcinoma. Ann Surg Oncol. 24:1037–1045. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Ma NF, Hu L, Fung JM, Xie D, Zheng BJ, Chen L, Tang DJ, Fu L, Wu Z, Chen M, et al: Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma. Hepatology. 47:503–510. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Cheng W, Su Y and Xu F: CHD1L: A novel oncogene. Mol Cancer. 12:1702013. View Article : Google Scholar : PubMed/NCBI

8 

Chen L, Yuan YF, Li Y, Chan TH, Zheng BJ, Huang J and Guan XY: Clinical significance of CHD1L in hepatocellular carcinoma and therapeutic potentials of virus-mediated CHD1L depletion. Gut. 60:534–543. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Wu J, Zong Y, Fei X, Chen X, Huang O, He J, Chen W, Li Y, Shen K and Zhu L: Presence of CHD1L over-expression is associated with aggressive tumor biology and is a novel prognostic biomarker for patient survival in human breast cancer. PLoS One. 9:e986732014. View Article : Google Scholar : PubMed/NCBI

10 

Su Z, Zhao J, Xian G, Geng W, Rong Z, Wu Y and Qin C: CHD1L is a novel independent prognostic factor for gastric cancer. Clin Transl Oncol. 16:702–707. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Su FR, Ding JH, Bo L and Liu XG: Chromodomain helicase/ATPase DNA binding protein 1-like protein expression predicts poor prognosis in nasopharyngeal carcinoma. Exp Ther Med. 8:1745–1750. 2014. View Article : Google Scholar : PubMed/NCBI

12 

He WP, Zhou J, Cai MY, Xiao XS, Liao YJ, Kung HF, Guan XY, Xie D and Yang GF: CHD1L protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival. BMC Cancer. 12:4372012. View Article : Google Scholar : PubMed/NCBI

13 

Farges O, Fuks D, Le Treut YP, Azoulay D, Laurent A, Bachellier P, Nuzzo G, Belghiti J, Pruvot FR and Regimbeau JM: AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectable intrahepatic cholangiocarcinoma. Cancer. 117:2170–2177. 2011. View Article : Google Scholar : PubMed/NCBI

14 

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

15 

Renshaw S: Immunohistochemistry and immunocytochemistry: Essential methods. John Wiley Sons. 6:2482017.

16 

Li J, Guan HY, Gong LY, Song LB, Zhang N, Wu J, Yuan J, Zheng YJ, Huang ZS and Li M: Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival. Clin Cancer Res. 14:6996–7003. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Koya Y, Kajiyama H, Liu W, Shibata K, Senga T and Kikkawa F: Murine experimental model of original tumor development and peritoneal metastasis via orthotopic inoculation with ovarian carcinoma cells. J Vis Exp. 9:543532016.

18 

Shu YJ, Weng H, Ye YY, Hu YP, Bao RF, Cao Y, Wang XA, Zhang F, Xiang SS, Li HF, et al: SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway. Mol Cancer. 14:122015. View Article : Google Scholar : PubMed/NCBI

19 

Tian F, Xu F, Zhang ZY, Ge JP, Wei ZF, Xu XF and Cheng W: Expression of CHD1L in bladder cancer and its influence on prognosis and survival. Tumor Biol. 34:3687–3690. 2013. View Article : Google Scholar

20 

Ji X, Li J, Zhu L, Cai J, Zhang J, Qu Y, Zhang H, Liu B, Zhao R and Zhu Z: CHD1L promotes tumor progression and predicts survival in colorectal carcinoma. J Surg Res. 185:84–91. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Zhong D, He G, Zhao S, Li J, Lang Y, Ye W, Li Y, Jiang C and Li X: LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway. Acta Histochem. 117:551–558. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Xu X, He Y, Miao X, Wu Y, Han J, Wang Q, Liu J, Zhong F, Ou Y, Wang Y and He S: Cell adhesion induces overexpression of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) and contributes to cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma cells. Leuk Res. 47:54–62. 2016. View Article : Google Scholar : PubMed/NCBI

23 

He LR, Ma NF, Chen JW, Li BK, Guan XY, Liu MZ and Xie D: Overexpression of CHD1L is positively associated with metastasis of lung adenocarcinoma and predicts patients poor survival. Oncotarget. 6:31181–31190. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Liu C, Fu X, Zhong Z, Zhang J, Mou H, Wu Q, Sheng T, Huang B and Zou Y: CHD1L expression increases tumor progression and acts as a predictive biomarker for poor prognosis in pancreatic cancer. Dig Dis Sci. 62:2376–2385. 2017. View Article : Google Scholar : PubMed/NCBI

25 

He Q, Cai L, Shuai L, Li D, Wang C, Liu Y, Li X, Li Z and Wang S: Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21. Mol Carcinog. 52:286–296. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Yang XQ, Xu YF, Guo S, Liu Y, Ning SL, Lu XF, Yang H and Chen YX: Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma. World J Gastroenterol. 20:4076–4084. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Shen G, Lin Y, Yang X, Zhang J, Xu Z and Jia H: MicroRNA-26b inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting USP9X. BMC Cancer. 14:3932014. View Article : Google Scholar : PubMed/NCBI

28 

Green DR and Chipuk JE: p53 and metabolism: Inside the TIGAR. Cell. 126:30–32. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Zolota V, Sirinian C, Melachrinou M, Symeonidis A and Bonikos DS: Expression of the regulatory cell cycle proteins p21, p27, p14, p16, p53, mdm2, and cyclin E in bone marrow biopsies with acute myeloid leukemia. Correlation with patients' survival. Pathol Res Pract. 203:199–207. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Chen M, Huang JD, Hu L, Zheng BJ, Chen L, Tsang SL and Guan XY: Transgenic CHD1L expression in mouse induces spontaneous tumors. PLoS One. 4:e67272009. View Article : Google Scholar : PubMed/NCBI

31 

López-Soto A, Gonzalez S, Smyth MJ and Galluzzi L: Control of metastasis by NK cells. Cancer Cell. 32:135–154. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Zhou W, Ye XL, Xu J, Cao MG, Fang ZY, Li LY, Guan GH, Liu Q, Qian YH and Xie D: The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b. Sci Signal. 10:eaak95572017. View Article : Google Scholar : PubMed/NCBI

33 

Kang Y and Massagué J: Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 118:277–279. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Chen L, Chan TH, Yuan YF, Hu L, Huang J, Ma S, Wang J, Dong SS, Tang KH, Xie D, et al: CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest. 120:1178–1191. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

August 2019
Volume 42 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Li, S., Chai, Y., Ding, Y., Yuan, T., Wu, C., & Huang, C. (2019). CHD1L is associated with poor survival and promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma. Oncology Reports, 42, 657-669. https://doi.org/10.3892/or.2019.7174
MLA
Li, S., Chai, Y., Ding, Y., Yuan, T., Wu, C., Huang, C."CHD1L is associated with poor survival and promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma". Oncology Reports 42.2 (2019): 657-669.
Chicago
Li, S., Chai, Y., Ding, Y., Yuan, T., Wu, C., Huang, C."CHD1L is associated with poor survival and promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma". Oncology Reports 42, no. 2 (2019): 657-669. https://doi.org/10.3892/or.2019.7174