Endocan silencing induces programmed cell death in hepatocarcinoma

Yang,Jinghui; Sheng,Shihou; Yang,Qiwei; Li,Li; Qin,Shaoyou; Yu,Shan; Zhang,Xuewen

doi:10.3892/ol.2017.6857

Endocan silencing induces programmed cell death in hepatocarcinoma

Authors:
- Jinghui Yang
- Shihou Sheng
- Qiwei Yang
- Li Li
- Shaoyou Qin
- Shan Yu
- Xuewen Zhang
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Affiliations: Department of Hepatopancreatobiliary Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Colorectal & Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Central Laboratory, Second Hospital, Jilin University, Changchun, Jilin 130041, P.R. China, Department of Respiratory Medicine, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Digestive Internal Medicine, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Neurology, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: August 31, 2017 https://doi.org/10.3892/ol.2017.6857
Pages: 5333-5339
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocarcinoma is a type of high‑grade malignant carcinoma identified worldwide. Its rapid development and late diagnosis prevents effective tumor resection in the majority of patients, and therefore recent studies have targeted metabolic signaling pathways and the tumor microenvironment for potential treatments. To investigate whether endocan may be a gene target for hepatocarcinoma treatment, the present study employed the following measures: MTT and Transwell assays, flow cytometry, western blotting and an mRFP‑GFP‑LC3 double fluorescence system. Following endocan gene silencing, cell proliferation was significantly inhibited and the number of invasive cells in the endocan siRNA‑treated group was reduced compared with the control‑siRNA treated‑group. Furthermore, the apoptosis rate was 15% and autophagy was detected in the endocan short interfering (si)RNA‑treated group compared with the control‑siRNA treated‑group. Using western blotting to detect NF‑κB expression in the nucleus, the NF‑κB expression was identified to be significantly reduced in the siRNA‑treated group compared with the control groups. Endocan gene silencing inhibited hepatocarcinoma cell viability and invasion, whilst inducing apoptosis and autophagy. The results of the present study suggest that the effect of endocan gene silencing on cell survival was mediated via the NF‑κB signaling pathway.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Song MJ and Bae SH: Newer treatments for advanced hepatocellular carcinoma. Korean J Intern Med. 29:149–155. 2014. View Article : Google Scholar : PubMed/NCBI
3	Abid MR, Yi XJ, Yano K, Shih SC and Aird WC: Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 72:136–145. 2006. View Article : Google Scholar : PubMed/NCBI
4	Maurage CA, Adam E, Minéo JF, Sarrazin S, Debunne M, Siminski RM, Baroncini M, Lassalle P, Blond S and Delehedde M: Endocan expression and localization in human glioblastomas. J Neuropathol Exp Neurol. 68:633–641. 2009. View Article : Google Scholar : PubMed/NCBI
5	Ziol M, Sutton A, Calderaro J, Barget N, Aout M, Leroy V, Blanc JF, Sturm N, Bioulac-Sage P, Nahon P, et al: ESM-1 expression in stromal cells is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma. J Hepatol. 59:1264–1270. 2013. View Article : Google Scholar : PubMed/NCBI
6	Oltean S, Pullerits R, Flodén A, Olausson M and Oltean M: Increased resistin in brain dead organ donors is associated with delayed graft function after kidney transplantation. J Transl Med. 11:2332013. View Article : Google Scholar : PubMed/NCBI
7	Leroy X, Aubert S, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin MC and Lassalle P: Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology. 56:180–187. 2010. View Article : Google Scholar : PubMed/NCBI
8	Zuo L, Zhang SM, Hu RL, Zhu HQ, Zhou Q, Gui SY, Wu Q and Wang Y: Correlation between expression and differentiation of endocan in colorectal cancer. World J Gastroenterol. 14:4562–4568. 2008. View Article : Google Scholar : PubMed/NCBI
9	Scherpereel A, Gentina T, Grigoriu B, Sénéchal S, Janin A, Tsicopoulos A, Plénat F, Béchard D, Tonnel AB and Lassalle P: Overexpression of endocan induces tumor formation. Cancer Res. 63:6084–6089. 2003.PubMed/NCBI
10	Kang YH, Ji NY, Lee CI, Lee HG, Kim JW, Yeom YI, Kim DG, Yoon SK, Kim JW, Park PJ and Song EY: ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma. Amino Acids. 40:1003–1013. 2011. View Article : Google Scholar : PubMed/NCBI
11	Chen LY, Liu X, Wang SL and Qin CY: Over-expression of the Endocan gene in endothelial cells from hepatocellular carcinoma is associated with angiogenesis and tumour invasion. J Int Med Res. 38:498–510. 2010. View Article : Google Scholar : PubMed/NCBI
12	Huang GW, Tao YM and Ding X: Endocan expression correlated with poor survival in human hepatocellular carcinoma. Dig Dis Sci. 54:389–394. 2009. View Article : Google Scholar : PubMed/NCBI
13	Gerritsen ME, Tomlinson JE, Zlot C, Ziman M and Hwang S: Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells. Br J Pharmacol. 140:595–610. 2003. View Article : Google Scholar : PubMed/NCBI
14	Kim JH, Park MY, Kim CN, Kim KH, Kang HB, Kim KD and Kim JW: Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1α in human colon carcinoma: Impact of ESM-1 on prognosis and its correlation with clinicopathological features. Oncol Rep. 28:1701–1708. 2012. View Article : Google Scholar : PubMed/NCBI
15	Kepp O, Galluzzi L, Lipinski M, Yuan J and Kroemer G: Cell death assays for drug discovery. Nat Rev Drug Discov. 10:221–237. 2011. View Article : Google Scholar : PubMed/NCBI
16	Jardon MA, Rothe K, Bortnik S, Vezenkov L, Jiang X, Young RN, Lum JJ and Gorski SM: Autophagy: From structure to metabolism to therapeutic regulation. Autophagy. 9:2180–2182. 2013. View Article : Google Scholar : PubMed/NCBI
17	Huang R and Liu W: Identifying an essential role of nuclear LC3 for autophagy. Autophagy. 11:852–853. 2015. View Article : Google Scholar : PubMed/NCBI
18	Lai SC and Devenish RJ: LC3-associated phagocytosis (LAP): Connections with host autophagy. Cells. 1:396–408. 2012. View Article : Google Scholar : PubMed/NCBI
19	Codogno P and Meijer AJ: Atg5: More than an autophagy factor. Nat Cell Biol. 8:1045–1047. 2006. View Article : Google Scholar : PubMed/NCBI
20	Huang X, Qi Q, Hua X, Li X, Zhang W, Sun H, Li S, Wang X and Li B: Beclin 1, an autophagy-related gene, augments apoptosis in U87 glioblastoma cells. Oncology Rep. 31:1761–1767. 2014. View Article : Google Scholar
21	Criollo A, Dessen P and Kroemer G: DRAM: A phylogenetically ancient regulator of autophagy. Cell Cycle. 8:2319–2320. 2009. View Article : Google Scholar : PubMed/NCBI
22	Hu X, Nesic-Taylor O, Qiu J, Rea HC, Fabian R, Rassin DK and Perez-Polo JR: Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. J Neurochem. 93:26–37. 2005. View Article : Google Scholar : PubMed/NCBI
23	Karin M, Yamamoto Y and Wang QM: The IKK NF-kappa B system: A treasure trove for drug development. Nat Rev Drug Discov. 3:17–26. 2004. View Article : Google Scholar : PubMed/NCBI
24	Tato CM and Hunter CA: Host-pathogen interactions: Subversion and utilization of the NF-kappa B pathway during infection. Infect Immun. 70:3311–3317. 2002. View Article : Google Scholar : PubMed/NCBI
25	Bai X, Feldman NE, Chmura K, Ovrutsky AR, Su WL, Griffin L, Pyeon D, McGibney MT, Strand MJ, Numata M, et al: Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages. PLoS One. 8:e619252013. View Article : Google Scholar : PubMed/NCBI
26	Loeuillet C, Martinon F, Perez C, Munoz M, Thome M and Meylan PR: Mycobacterium tuberculosis subverts innate immunity to evade specific effectors. J Immunol. 177:6245–6255. 2006. View Article : Google Scholar : PubMed/NCBI
27	Karin M, Cao Y, Greten FR and Li ZW: NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI
28	Fukuda M, Kusama K and Sakashita H: Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression. BMC Cancer. 8:3762008. View Article : Google Scholar : PubMed/NCBI
29	Djavaheri-Mergny M, Amelotti M, Mathieu J, Besançon F, Bauvy C, Souquère S, Pierron G and Codogno P: NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy. J Biol Chem. 281:30373–30382. 2006. View Article : Google Scholar : PubMed/NCBI
30	Peri S, Devarajan K, Yang DH, Knudson AG and Balachandran S: Meta-analysis identifies NF-κB as a therapeutic target in renal cancer. PLoS One. 8:e767462013. View Article : Google Scholar : PubMed/NCBI
31	Orlowski RZ and Baldwin AS Jr: NF-kappaB as a therapeutic target in cancer. Trends Mol Med. 8:385–389. 2002. View Article : Google Scholar : PubMed/NCBI