STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

Wang, Hui; Huo, Xisong; Yang, Xun; He, Jia; Liu, Cheng; Wang, Na; Deng, Xuan; Jin, Haojie; Wang, Ning; Wang, Cun; Zhao, Fangyu; Fang, Jing‐Yuan; Yao, Ming; Fan, Jia; Qin, Wenxin

doi:10.1186/s12943-017-0680-1

Cited by 454 publications

(376 citation statements)

References 52 publications

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“…In experiments investigating the underlying mechanism, PRMT1 accelerated HCC through the STAT3 pathway at the mRNA and protein levels. We also found that upregulating PRMT1 can increase STAT3 phosphorylation and thereby activate the STAT3 pathway, which can potentiate the development of HCC [22][23][24][25][26][27]. Finally, cryptotanshinone, a STAT3 inhibitor, suppressed HCC growth and migration through inhibiting STAT3 phosphorylation, which was activated by PRMT1 overexpression.…”

Section: Discussionmentioning

confidence: 60%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although it has been widely accepted that protein arginine methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration. This study aimed to investigate the role of PRMT1 in HCC growth and metastasis. Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses. Cell proliferation, colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT, crystal violet and Boyden chamber assays. Tumour growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and recurrence; PRMT1 expression was also positively correlated with microvascular invasion (P = 0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo, as well as tumour metastasis. These phenotypes were associated with STAT3 signalling pathway activation. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. Conclusions: We revealed a significant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation. PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 60%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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“…Increasing literatures have confirmed that ceRNAs play key roles in many biological processes and immune responses [34,35], and miRNAs have been documented to be involved in the regulation of macrophage polarization [36,37] , similar to lncRNAs [14][15][16]. We were interested in identifying whether an mRNA-related ceRNA network existed during F. gigantica ESP-induced M2 cell polarization into M1 cells.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

Luo

Zhang

Sheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. Methods: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. Results: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. Conclusions: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.

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“…Additionally, HOTAIR is associated with breast and liver cancer (30). HOTAIR is markedly reduced in lung cancer tissues, reinforcing the concept that the HOTAIR gene may have an important function in lung cancer (31). HOXD10 is another gene that is associated with cancer (30).…”

Section: Discussionmentioning

confidence: 83%

“…Although there is no clear difference in HOXD10 expression in cancerous tissues and healthy tissues, the gene has been revealed to be associated with lymphatic metastasis (32). Additionally, HOXD10 expression has been significantly increased in cancer tissues with lymphatic metastases (31). An in vitro experiment indicated that HOXD10 is modulated by the HOTAIR gene (10).…”

Section: Discussionmentioning

confidence: 99%

Anticancer effect of HOTTIP regulates human pancreatic cancer via the metabotropic glutamate receptor 1 pathway

Li²,

Wei

et al. 2018

Oncol Lett

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Abstract. The present study aimed to determine how the expression and function of HOTTIP modifies, and regulates the metabotropic glutamate receptor 1 (mGluR1) to affect human pancreatic cancer cell viability. HOTTIP expression was higher in human pancreatic cancer tissue compared with in para-carcinoma tissue. However, downregulation of HOTTIP expression was revealed to significantly reduce cell viability, induce apoptosis, promote caspase-3 and caspase-8 activities and increase Bax expression in pancreatic cancer cells. Additionally, downregulation of HOTTIP expression significantly suppressed mGluR1 and mitigated activation of the phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway in pancreatic cancer cells. To the best of our knowledge, the present study is the first to identify that the anticancer effect of HOTTIP against human pancreatic cancer functions the mGluR1 pathway.

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STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4

Cited by 454 publications

References 52 publications

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

Anticancer effect of HOTTIP regulates human pancreatic cancer via the metabotropic glutamate receptor 1 pathway

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