Expression of Intercellular Adhesion Molecule 1 by Hepatocellular Carcinoma Stem Cells and Circulating Tumor Cells

Liu, Shupeng; Li, Nan; Yu, Xiuchong; Xiao, Xiao; Cheng, Kai; Hu, Jingjing; Wang, Jiaqi; Zhang, Dandan; Cheng, Shuqun

doi:10.1053/j.gastro.2013.01.046

Cited by 166 publications

(125 citation statements)

References 37 publications

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“…Among the differentially expressed molecules, further analyses revealed that an lncRNA had approximately 800 bp complementary to the ICAM-1 mRNA sequence, thus termed as ICAM-1-related (ICR) lncRNA. ICR formed an RNA duplex with ICAM-1 to maintain ICAM-1 expression, thereby regulating the stem cell properties of ICAM-1 þ HCC cells, as ICAM-1 was previously observed to be a CSC marker in HCC (20). In addition, retrospective and prospective analyses revealed that ICR expression was closely associated with PVTT development and HCC patients' prognosis.…”

Section: Introductionmentioning

confidence: 85%

“…The cell lines were maintained in high-glucose DMEM (Gibco BRL) supplemented with 10% FBS (Gibco BRL), 100 mg/mL penicillin G, and 50 mg/mL streptomycin (Gibco BRL) at 37 C in a humidified atmosphere containing 5% CO 2 . At the beginning of this study, all the 3 cell lines were authenticated through testing the expression of a-fetoprotein and cytokeratin 19 by flow cytometry as what we did before in our previously study (20).…”

Section: Cell Linesmentioning

confidence: 99%

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ICAM-1–Related Noncoding RNA in Cancer Stem Cells Maintains ICAM-1 Expression in Hepatocellular Carcinoma

Guo

Liu

Cheng

et al. 2016

Clinical Cancer Research

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Purpose: Portal vein tumor thrombus (PVTT) is a major complication of hepatocellular carcinoma (HCC) and is associated with poor survival. Long noncoding RNAs (lncRNA) contribute to HCC metastasis, but whether and how lncRNAs affect PVTT development remains unclear. In the present study, a novel highly expressed lncRNA (ICAM-1-related, ICR) was identified in ICAM-1 þ cancer stem cells (CSC) in HCC. This lncRNA regulated CSC properties and contributed to PVTT development.Experimental Design: We used microarray and bioinformatics analyses to identify differentially expressed lncRNAs. Realtime PCR and Western blotting were used to assess gene expression in cell lines and tumors. Sphere formation assays were performed to investigate stem cell properties of tumor cells in vitro. Retrospective and prospective studies were used to investigate the relationship between ICR expression and clinical outcomes. Conclusions: Our study demonstrates that ICR specifically regulates CSC properties of ICAM-1 þ HCC cells and that ICR contributes to PVTT development. Therefore, ICR may be a promising target for HCC therapy.

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Section: Introductionmentioning

confidence: 85%

Section: Cell Linesmentioning

confidence: 99%

ICAM-1–Related Noncoding RNA in Cancer Stem Cells Maintains ICAM-1 Expression in Hepatocellular Carcinoma

Guo

Liu

Cheng

et al. 2016

Clinical Cancer Research

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“…Further studies will be required to investigate whether the hepatocarcinogenesis process, which is mediated by HBVinduced ROS accumulation, can be observed in HBV transgenic mice that mimic development of human HCC. 26 Materials and Methods Cell lines. HepG2, HepG2.2.15 and HepAD38 cells were cultivated in Dulbecco's modified Eagle's medium (Gibco, Grand Island, NY, USA) containing 10% FBS (Hyclone, Logan, UT, USA), penicillin (10 7 U/l) and streptomycin (10 mg/l) at 37°C and 5% CO 2 .…”

Section: Discussionmentioning

confidence: 99%

HBV-induced ROS accumulation promotes hepatocarcinogenesis through Snail-mediated epigenetic silencing of SOCS3

Yuan

et al. 2016

Cell Death Differ

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Interleukin-6 (IL-6) has been demonstrated to be involved in Hepatitis B virus (HBV)-associated hepatocarcinogenesis through activation of the STAT3 pathway. The sustained activation of the IL-6/STAT3 pathway is frequently associated with repression of SOCS3, which is both a target gene and a negative regulator of STAT3. However, the silencing mechanism of SOCS3 in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we showed that the repression of SOCS3 and sustained activation of IL-6/STAT3 pathway in HBV-producing HCC cells were caused by HBV-induced mitochondrial ROS accumulation. Mechanistic studies revealed that ROS-mediated DNA methylation resulted in the silencing of SOCS3. Decreased SOCS3 expression significantly promoted the proliferation of HCC cells and growth of tumor xenografts in mice. Further studies revealed that HBVinduced ROS accumulation upregulated the expression of the transcription factor, Snail, which bound to the E-boxes of SOCS3 promoter and mediated the epigenetic silencing of SOCS3 in association with DNMT1 and HDAC1. In addition, we found that the expression of Snail and SOCS3 were inversely correlated in HBV-associated HCC patients, suggesting that SOCS3 and/or Snail could be used as prognostic markers in HCC pathogenesis. Taken together, our data show that HBV-induced mitochondrial ROS production represses SOCS3 expression through Snail-mediated epigenetic silencing, leading to the sustained activation of IL-6/STAT3 pathway and ultimately contributing to hepatocarcinogenesis. Cell Death and Differentiation (2016) 23, 616-627; doi:10.1038/cdd.2015.129; published online 22 January 2016 Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer death in the world.1 Chronic HBV infection and chronic liver disease that progress from hepatitis to cirrhosis are major risk factors for the development of HCC. Options for the treatment of HCC are quite limited because the molecular, cellular and environmental mechanisms that drive HBV-associated HCC pathogenesis are poorly understood.Pro-inflammatory cytokines contribute significantly to the pathogenesis of many tumor types.2 Among them, elevated IL-6 is closely related to HCC development and progression.3 Elevated IL-6 was found in patients with viral and alcoholic hepatitis and liver cirrhosis. In these conditions, IL-6 is expressed mainly by myeloid cells/leukocytes. 4 Recent studies have confirmed that upregulation of IL-6 in human HCC, where it is expressed by the cancer cells, also has a central role in a gene expression network via an autocrine signaling pathway that drives tumor development and progression.5 However, it remains unknown whether IL-6 autocrine signaling can be stimulated by HBV during hepatocarcinogensis.Reactive oxygen species (ROS) are continuously generated by cells to regulate cellular responses such as proliferation, differentiation and apoptosis. 6 Chronic virus infection may enhance ROS production and cause oxidative stress in host cells.7 Continued oxidative...

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“…S4D-S4G). With regard to IFNg-STAT1 pathway genes, ICAM1 is involved in sphere formation and metastatic potential (46), and increased expression at invasive fronts is positively correlated with invasion and metastasis (47). SMAD7 is involved in tumorigenesis of mesenchymal stem cells concomitant with upregulation of MYC under prolonged inflammatory IFNg exposure (48).…”

Section: Discussionmentioning

confidence: 99%

STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer

et al. 2014

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Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease. Cancer Res; 74(22); 6519-30. Ó2014 AACR.

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Expression of Intercellular Adhesion Molecule 1 by Hepatocellular Carcinoma Stem Cells and Circulating Tumor Cells

Cited by 166 publications

References 37 publications

ICAM-1–Related Noncoding RNA in Cancer Stem Cells Maintains ICAM-1 Expression in Hepatocellular Carcinoma

ICAM-1–Related Noncoding RNA in Cancer Stem Cells Maintains ICAM-1 Expression in Hepatocellular Carcinoma

HBV-induced ROS accumulation promotes hepatocarcinogenesis through Snail-mediated epigenetic silencing of SOCS3

STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer

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