Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1

Zhang, Jun; Jin, Hongyu; Wu, Yunhao; Zheng, Zhihong; Guo, Shuai; Wang, Y.; Yang, Dong; Meng, Xiangyu; Xu, Xiaoman; Zhao, Yan

doi:10.1007/s12094-019-02035-9

Cited by 63 publications

(45 citation statements)

References 28 publications

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“…Thus, these findings support the role of the lnc-NEAT1/miR-199a-3p/UCK2 axis in HCC tumor growth in vivo. reported that lncRNA-PCGEM1 is induced in GC cells under hypoxic conditions and acts as an oncogenic factor [15], while up-regulation of lncRNA-BX111 in response to hypoxia promotes metastasis and progression of pancreatic cancer [9]. In the present study, we confirmed the response of lncRNA-NEAT1 to hypoxia and demonstrated that lncRNA-NEAT1 is transcriptionally regulated by HIF-1α in HCC cells.…”

Section: Lncrna-neat1 Promotes Hcc Tumor Growth Through Mir-199a-3p/usupporting

confidence: 82%

Hypoxia-induced lncRNA -NEAT1 sustains the growth of hepatocellular carcinoma via regulation of miR-199a-3p/UCK2: integrative bioinformatics analysis and experimental validation

Zhang

Qian²,

Xia

et al. 2020

Preprint

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Background: The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. However, it remains unclear whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function is not well characterized. Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA -NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo . Results : LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. Furthermore, lncRNA-NEAT1 was demonstrated to serve as a miR-199a-3p sponge that regulates UCK2 expression and to play a tumor-suppressive role in HCC, while UCK2 promotes cell growth. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model. Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC that sustains the growth of HCC cells by regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC.

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Section: Lncrna-neat1 Promotes Hcc Tumor Growth Through Mir-199a-3p/usupporting

confidence: 82%

Hypoxia-induced lncRNA -NEAT1 sustains the growth of hepatocellular carcinoma via regulation of miR-199a-3p/UCK2: integrative bioinformatics analysis and experimental validation

Zhang

Qian²,

Xia

et al. 2020

Preprint

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“…By forming a complex with HIF-1α, lncHIFCAR/MIR31HG promotes the binding of HIF-1α to the target promoters and increases the sphere-forming and metastatic ability of oral cancer cells (66). lncRNA PCGEM1 may be used as a scaffold to form a complex with HIF-1α and transcription factor Snail homolog 1 (SNAI1) and regulate the invasion and metastasis of gastric cancer cells (67). Hypoxia-induced lncRNA CRPAT4 is regulated by HIF-1α and plays a carcinogenic role by promoting the growth and migration of cancer cells (68).…”

Section: Role Of Hif-1 In Non-coding Rna Associated With Cscsmentioning

confidence: 99%

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

et al. 2020

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Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo-, radio-and immuno-resistance. Understanding the mechanism of CSC self-renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial-mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor-1 (HIF-1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF-1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non-coding RNA and signaling pathways associated with HIF-1, in order to provide novel targets with HIF-1 as the core for clinical treatment, and extend the life of patients. Contents 1. Introduction 2. Structural characteristics of HIF-1 3. Role of epigenetic and post-translational modification of HIF-1 in CSCs 4. Role of HIF-1 in non-coding RNA associated with CSCs 5. Role of HIF-1 in CSC markers 6. Role of HIF-1 in tumor immunity of CSCs 7. Role of HIF-1 in metabolic reprogramming of CSCs 8. Role of HIF-1 in signaling pathways associated with CSCs 9. Potential targets for CSC therapy 10. Conclusions and perspectives

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“…Therefore, hypoxic conditions induce HIF-1α, BC005927, and EPHB4 expression in GC cells, resulting in increased metastasis. Another hypoxia-induced lncRNA, prostate cancer gene expression marker 1 (PCGEM1), has also been identified in GC [41]. PCGEM1 is also overexpressed in GC tissues and its expression is upregulated by hypoxia in GC cells, with PCGEM1 knockdown significantly repressing GC cell invasion and metastasis.…”

Section: Hifs Regulate Ncrna Expression In Gcmentioning

confidence: 99%

“…Regulates GC cell invasion, metastasis, and EMT SNAI1 [41] GAPLINC Upregulated in GC and is associated with poor prognosis (HRE region in lncRNA promoter 1 ) [42] AK123072…”

Section: Pcgem1mentioning

confidence: 99%

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

Cho

Han

Hur

et al. 2019

Genes

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Hypoxia-inducible factors (HIFs) are transcription factors that play central roles in cellular responses against hypoxia. In most cancers, HIFs are closely associated with tumorigenesis by regulating cell survival, angiogenesis, metastasis, and adaptation to the hypoxic tumor microenvironment. Recently, non-coding RNAs (ncRNAs) have been reported to play critical roles in the hypoxic response in various cancers. Here, we review the roles of hypoxia-response ncRNAs in gastrointestinal cancer, with a particular focus on microRNAs and long ncRNAs, and discuss the functional relationships and regulatory mechanisms between HIFs and ncRNAs.

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Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1

Cited by 63 publications

References 28 publications

Hypoxia-induced lncRNA -NEAT1 sustains the growth of hepatocellular carcinoma via regulation of miR-199a-3p/UCK2: integrative bioinformatics analysis and experimental validation

Hypoxia-induced lncRNA -NEAT1 sustains the growth of hepatocellular carcinoma via regulation of miR-199a-3p/UCK2: integrative bioinformatics analysis and experimental validation

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

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