HOTAIR Long Noncoding RNA Promotes Gastric Cancer Metastasis through Suppression of Poly r(C)-Binding Protein (PCBP) 1

Zhang, Zizhen; Shen, Zhiyong; Shen, Yanying; Zhao, Enyue; Wang, Ming; Wang, Chaojie; Cao, Hui; Xu, Jia

doi:10.1158/1535-7163.mct-14-0695

Cited by 106 publications

(90 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fifteen percent to 18% of somatic promoters mapped to noncoding RNAs, including HOTAIR and PVT1, previously associated with gastric cancer (Supplementary Table S3; refs. 52,53). Additional analyses at increasing thresholds of stringency (FC from 1.5 to 2 and FDR from 0.1 to 0.001) yielded similar results, supporting the robustness of this analysis ( Supplementary Fig.…”

Section: Identifying Epigenomic Promoter Alterations In Gastric Cancersupporting

confidence: 74%

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

Promoter elements play important roles in isoform and cell type-specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and nonmalignant gastric tissues. We identified nearly 2,000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3). Somatic promoterassociated N-terminal peptides displaying relative depletion in tumors exhibited high-affinity MHC binding predictions and elicited potent T-cell responses in vitro, suggesting a mechanism for reducing tumor antigenicity. In multiple patient cohorts, gastric cancers with high somatic promoter usage also displayed reduced T-cell cytolytic marker expression. Somatic promoters are enriched in PRC2 occupancy, display sensitivity to EZH2 therapeutic inhibition, and are associated with novel cancer-associated transcripts. By generating tumor-specific isoforms and decreasing tumor antigenicity, epigenomic promoter alterations may thus drive intrinsic tumorigenesis and also allow nascent cancers to evade host immunity. SIGNIFICANCE:We apply epigenomic profiling to demarcate the promoter landscape of gastric cancer. Many tumor-specific promoters activate different promoters in the same gene, some generating pro-oncogenic isoforms. Tumor-specific promoters also reduce tumor antigenicity by causing relative depletion of immunogenic peptides, contributing to cancer immunoediting and allowing tumors to evade host immune attack. Cancer Discov; 7(6);

show abstract

Section: Identifying Epigenomic Promoter Alterations In Gastric Cancersupporting

confidence: 74%

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

show abstract

“…For instance, lncRNA HOTAIR promotes gastric cancer metastasis through inhibition of Poly r(C) Binding Protein (PCBP) 1 (35). In our previous studies, we found that p53-regulated lncRNA TUG1 affected NSCLC cell proliferation via epigenetically regulating HOXB7 expression.…”

Section: Discussionmentioning

confidence: 96%

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

Wan

Sun

Liu

et al. 2016

Molecular Cancer Therapeutics

209

180

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNA) are a novel class of transcripts with no protein coding capacity, but with diverse functions in cancer cell proliferation, apoptosis, and metastasis. The lncRNA PVT1 is 1,716 nt in length and located in the chr8q24.21 region, which also contains the myelocytomatosis (MYC) oncogene. Previous studies demonstrated that MYC promotes PVT1 expression in primary human cancers. However, the expression pattern and potential biologic function of PVT1 in non-small cell lung cancer (NSCLC) is still unclear. Here, we found that PVT1 was upregulated in 105 human NSCLC tissues compared with normal samples. High expression of PVT1 was associated with a higher tumor-node-metastasis stage and tumor size, as well as poorer overall survival. Functional analysis revealed that knockdown of PVT1 inhibited NSCLC cell proliferation and induced apoptosis both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that PVT1 recruits EZH2 to the large tumor suppressor kinase 2 (LATS2) promoter and represses LATS2 transcription. Furthermore, ectopic expression of LATS2 increased apoptosis and repressed lung adenocarcinoma cell proliferation by regulating the Mdm2-p53 pathway. Taken together, our findings indicated that PVT1/EZH2/LATS2 interactions might serve as new target for lung adenocarcinoma diagnosis and therapy.

show abstract

“…Abnormal lncRNAs or miRNAs expression and their associations with occurrence of multiple cancers have been studied in a variety of cancer cells [30][31][32]. Previous researches have been demonstrated the oncogenic roles of UCA1 in osteosarcoma [14,33].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

Xing

Gong

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Previous studies demonstrated the oncogenic roles of lncRNA UCA1 in osteosarcoma. This study aimed to explore the internal molecular mechanism of UCA1 on promoting osteosarcoma cell proliferation, migration and invasion. Methods: qRT-PCR was conducted to measure the expression levels of UCA1, miR-182 and TIMP2. Cell transfection was used to change the expression levels of UCA1, miR-182 and TIMP2. Cell viability, migration, invasion and apoptosis were measured using CCK-8 assay, two-chamber migration (invasion) assay and Guava Nexin assay, respectively. The associations between UCA1, miR-182 and iASPP were analyzed by dual luciferase activity assay. The protein expression levels of key factors involved in cell apoptosis, PI3K/AKT/GSK3β pathway and NF-κB pathway, as well as p53, Rb, RECQ family and iASPP were evaluated by western blotting. Results: UCA1 was highly expressed in osteosarcoma MG63 and OS-732 cells. Knockdown of UCA1 inhibited OS-732 cell viability, migration and invasion, but promoted cell apoptosis. miR-182 was up-regulated in OS-732 cells after UCA1 knockdown and participated in the effects of UCA1 on OS-732 cells. TIMP2 was downstream factor of miR-182 and involved in the regulatory roles of miR-182 on OS-732 cell viability, migration, invasion, apoptosis, as well as PI3K/AKT/GSK3β and NF-κB pathways. UCA1 knockdown up-regulated p53, Rb and RECQL5 levels in OS-732 cells, while down-regulated the expression of iASPP. TGF-β or TNF-α treatment could enhance the expression of UCA1 in OS-732 cells. Conclusion: Our research verified that UCA1 exerted oncogenic roles in osteosarcoma cells by regulating miR-182 and TIMP2, as well as PI3K/AKT/GSK3β and NF-κB pathways.

show abstract

HOTAIR Long Noncoding RNA Promotes Gastric Cancer Metastasis through Suppression of Poly r(C)-Binding Protein (PCBP) 1

Cited by 106 publications

References 28 publications

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

Contact Info

Product

Resources

About