HIF2-Induced Long Noncoding RNA RAB11B-AS1 Promotes Hypoxia-Mediated Angiogenesis and Breast Cancer Metastasis

Niu, Yanling; Bao, Lei; Chen, Yan; Wang, Chenliang; Luo, Maowu; Zhang, Bo; Zhou, Mi; Wang, Jennifer E.; Fang, Yisheng; Kumar, Ashwani; Xing, Chao; Wang, Yingfei; Luo, Weibo

doi:10.1158/0008-5472.can-19-1532

Cited by 140 publications

(110 citation statements)

References 28 publications

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“…Metastasis and angiogenesis are typical characteristics of breast cancer, which lead to poor prognosis, frequent recurrence and pronounced invasiveness [17]. Accumulating evidence has revealed that lncRNAs play an important role in the carcinogenesis and progression of breast cancer by in uencing critical events such as cell proliferation, metastasis, and angiogenesis [18]. In the present study, we rstly gured out a novel lncRNA PCDHB17P, which was highly expressed in breast cancer tissues and also associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 72%

LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop

Zhu

Zhang

Wang

et al. 2020

Preprint

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Background: Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood.Methods: TCGA data was utilized to screen out lncRNAs dysregulated in breast cancer. The expression level of genes were analyzed and measured by RT-qPCR. The effects of PCDHB17P in breast cancer were determined in vitro and in vivo. Bioinformatics analysis was applied to predict the target between genes in breast cancer and verified via luciferase reporter assays, RNA Immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP).Results: LncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decree ased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer.Conclusions: Our research demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

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Section: Discussionmentioning

confidence: 72%

LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop

Zhu

Zhang

Wang

et al. 2020

Preprint

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“…Previous studies have reported that in colorectal cancer, the novel primate‐specific lncRNA FLANC not only affects tumor growth but also participates in angiogenesis by regulating the STAT3/VEGF‐A axis 37 . In breast cancer lncRNA RAB11B‐AS1 was reported to be induced under hypoxia and facilitate the expression of angiogenic factors (eg, VEGF‐A and ANGPTL4) in breast cancer cells by facilitating recruitment of RNA polymerase II, leading to angiogenesis and metastasis in breast cancer 38 . Furthermore, regarding the relationship between p21 and vascular endothelial growth factor A (VEGF‐A), it was observed that when p21 levels increased, VEGF‐A expression decreased 39 .…”

Section: Discussionmentioning

confidence: 99%

lncRNA IGKJ2‐MALLP2 suppresses LSCC proliferation, migration, invasion, and angiogenesis by sponging miR‐1911‐3p/p21

Cao

Yang

et al. 2020

Cancer Science

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Because advanced laryngeal squamous cell carcinoma (LSCC) is diagnosed as a malignant tumor with a poor prognosis, the associated mechanisms still need to be further investigated. As key players in the development and progression of LSCC, lncRNAs have attracted increasing attention from many researchers. In this study, a novel lncRNA termed IGKJ2‐MALLP2 was identified and investigated for its effects on the development of LSCC. IGKJ2‐MALLP2 expression was confirmed by RT‐qPCR in 78 pairs of tissues and human laryngeal carcinoma cell lines. The results of this study showed that the expression of IGKJ2‐MALLP2 was reduced in LSCC tissues and displayed close relationships with tumor stage, lymph node metastasis, and clinical stage. Using a dual‐luciferase reporter assay, the ability of miR‐1911‐3p to bind both IGKJ2‐MALLP2 and p21 mRNA was demonstrated. IGKJ2‐MALLP2 could upregulate p21 expression by competitively binding miR‐1911‐3p. Moreover, IGKJ2‐MALLP2 effectively hindered the invasion, migration, and proliferation of AMC‐HN‐8 and TU212 tumor cells. Furthermore, its high expression could hinder the secretion of VEGF‐A and suppress angiogenesis. As revealed by the results of in vitro experiments, IGKJ2‐MALLP2 overexpression could restrict tumor growth and blood vessel formation in a xenograft model of LSCC. As indicated from the mentioned findings, IGKJ2‐MALLP2, which mediates p21 expression by targeting miR‐1911‐3p, was capable of regulating LSCC progression and could act as an underlying therapeutic candidate to treat LSCC.

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“…LncRNA ZFAS1 promotes angiogenesis via miR-150-5p/VEGFA signaling [165]. In breast cancer cells, lncRNA RAB11B-AS1 recruits RNA polymerase II to upregulate VEGFA and ANGPTL4 expression and promotes tumor angiogenesis [166]. In hepatocellular carcinoma cells, lncRNA HULC promotes angiogenesis via miR-107/E2F1/SPHK1 signaling [167].…”

Section: Non-coding Rnamentioning

confidence: 99%

The role of microenvironment in tumor angiogenesis

Jiang

Wang

Deng

et al. 2020

J Exp Clin Cancer Res

424

250

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Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor cells, surrounding cells, and secreted cytokines—provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome.

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HIF2-Induced Long Noncoding RNA RAB11B-AS1 Promotes Hypoxia-Mediated Angiogenesis and Breast Cancer Metastasis

Cited by 140 publications

References 28 publications

LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop

LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop

lncRNA IGKJ2‐MALLP2 suppresses LSCC proliferation, migration, invasion, and angiogenesis by sponging miR‐1911‐3p/p21

The role of microenvironment in tumor angiogenesis

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