A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma

Zhou, Bo; Chen, Hongxu; Dong, Wei; Kuang, Yi; Zhao, Xiao-biao; Li, Guangyao; Xie, Jun; Chen, Ping

doi:10.1186/1756-9966-33-55

Cited by 64 publications

(76 citation statements)

References 42 publications

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“…One of the hallmarks of inactivation of the JAK-STAT signaling pathway is the restriction in translocation of the nuclear and accumulated STAT3 in the cytoplasm [42]. Moreover, recent studies have revealed the importance of the JAK/STAT pathway in the development of HCC and have indicated that JAK/STAT inhibitors might be able to be used in the treatment of HCC [21,43].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

Tan

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. Methods: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. Results: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. Conclusion: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

Tan

Wang

et al. 2018

Cell Physiol Biochem

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“…The cells that had invaded into the bottom surface of the filter were fixed with methanol and stained with hematoxylin. The invasive ability was determined by counting the penetrating cells under a microscope at ×400 magnification on 5 random fields in each well [23]. …”

Section: Methodsmentioning

confidence: 99%

Mediation of the malignant biological characteristics of gastric cancer cells by the methylated CpG islands in RNF180 DNA promoter

Deng

Guo

et al. 2016

Oncotarget

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We previously demonstrated that the methylation of ring finger protein 180 (RNF180) DNA promoter was specific to gastric cancer tissues. We reported that four hypermethylated CpG islands, namely, CpG-116, CpG-80, CpG+97, and CpG+102, in RNF180 promoter were significantly associated with the postoperative overall survival of gastric cancer patients. Correlation analysis revealed that the methylated status of CpG islands was significantly associated with the lymph node metastasis of gastric cancer. We formulated four types of MGC-803 cells with the specific demethylation of one of the four CpG islands through vector transfection method. Conventional detections for the biological characteristics of cancer cells showed that 1) the methylation of CpG+102 island in RNF180 DNA promoter could remarkably influence the comprehensively malignant biological characteristics of gastric cancer cells, including their proliferation, invasion, cell cycle, anti-apoptosis, and tumorigenicity. 2) The CpG+97 island, in addition to the CpG+102 island, should be considered as the other key methylated locus in RNF180 DNA promoter to mediate the malignant biological characteristics of gastric cancer cells. The methylated status of the key CpG islands of RNF180 DNA promoter may be used to predict the variations of the malignant biological characteristics of gastric cancer cells. The proposed method is a promising molecular therapy for gastric cancer.

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“…Interestingly, Brachyury is located at 6q27, which is a frequently amplified region in HCC [12]. The function of Brachyury has extensively been characterized in mice and zebrafish [13,14].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma

et al. 2014

J Exp Clin Cancer Res

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Aims: Brachyury overexpression has been reported in various human malignant neoplasms, but its expression and function in hepatocellular carcinoma progression and metastasis remains unknown. The present study aimed to evaluate the critical role of Brachyury in HCC metastasis. Methods: The expression of Brachyury in human HCC (SMMC7721, HepG2, FHCC98, and Hep3B) and control cell lines was analyzed using quantitative reverse-transcriptase polymerase chain reaction and immunoflourence methods. Cancerous tissues collected from patients with HCC (n = 112) were analyzed using immunohistochemical method; a microarray analysis of HCC tissues was performed to explore the clinicopathological variables of HCC. The migratory and invasive capacities of Brachyury-SMMC7721 and Brachyury-HepG2 transfected cells were evaluated using in vitro scratch wound healing and Matrigel invasion assays, respectively. Further, six-week-old male BALB/c nude mice (n = 10) model was used in vivo assay.Results: Elevated expression of Brachyury was detected in HCCs (62.5%) compared with that in adjacent nontumorous tissues. Clinicopathological analysis revealed a close correlation of Brachyury expression with distant metastasis and poor prognosis of HCC. Overexpression of Brachyury promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Brachyury overexpression enhanced Akt activation by inhibiting phosphatase and tensin homolog (PTEN), which led to subsequent stabilization of Snail, a critical EMT mediator. Conclusion:The study findings suggest that elevated Brachyury facilitates HCC metastasis by promoting EMT via PTEN/Akt/Snail-dependent pathway. Brachyury plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.

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A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma

Cited by 64 publications

References 42 publications

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

Mediation of the malignant biological characteristics of gastric cancer cells by the methylated CpG islands in RNF180 DNA promoter

Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma

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