Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6

Xu, Xiaofang; Ge, Shengfang; Jia, Renbing; Zhou, Yixiong; Song, Xin; Zhang, He

doi:10.3892/or.2015.3900

Cited by 40 publications

(27 citation statements)

References 32 publications

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“…The upstream regulatory mechanism of PDCD10 remains unclear at present. Xu et al (29) found that miR-181b enhanced angiogenesis of retinoblastoma cells by targeting PDCD10. Wu et al (30) demonstrated that miR-613 could regulate cardiomyocyte apoptosis by targeting the PDCD10 gene.…”

Section: Discussionmentioning

confidence: 99%

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10

Jiang

et al. 2018

Oncol Rep

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MicroRNA (miR)-26a-5p and miR-26b-5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR-26a-5p and miR-26b-5p were lower than in paired normal tissues. The upregulation of miR-26-5p significantly inhibited the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) was the downstream target gene of miR-26a-5p/miR-26b-5p, and this was ascertained by western blotting and quantitative real-time reverse transcription PCR (RT-qPCR). In addition, in the 3'-UTR of PDCD10, the binding site was identified using a luciferase reporter assay. We determined that clinical BC tissues presented higher PDCD10 levels than adjacent normal tissues and that PDCD10 promoted proliferation of BC cell lines. Overexpression of miR-26a-5p/miR-26b-5p inhibited the stimulatory effect on proliferation of BC cells induced by PDCD10. In addition, in vivo experiments and clinical data revealed that the prognosis of BC patients with high expression of miR-26a-5p/miR-26b-5p and low expression of PDCD10 was better than that of patients with low miR-26-5p and high PDCD10 expression. These data revealed that miR-26a-5p and miR-26b-5p were pivotal regulators in BC progression by targeting the proliferation-related protein, PDCD10. The miR-26-5p/PDCD10 interaction may provide important insight into the pathway of BC progression and present novel opportunities for future diagnosis and treatment strategies, especially for patients with high levels of PDCD10.

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Section: Discussionmentioning

confidence: 99%

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10

Jiang

et al. 2018

Oncol Rep

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“…Retinoblastoma is the most common and malignant intraocular tumor in children, and hypoxia is one of the factors that influence the treatment of retinoblastoma. miR‐181b can promote angiogenic function in part by inhibiting the expression of GATA6, and therefore, it can serve as a new potential target for the treatment of retinoblastoma …”

Section: Gata6 and Human Cancersmentioning

confidence: 99%

“…miR-181b can promote angiogenic function in part by inhibiting the expression of GATA6, and therefore, it can serve as a new potential target for the treatment of retinoblastoma. 100 In addition, according to a recent study on cutaneous T-cell lymphoma (CTCL), GATA6 directly up-regulates CD137L expression and promotes tumor growth. 101 In a study of animal models of sebaceous gland (SG) tumors, Gata6 was found to control sebaceous gland development and cancer.…”

Section: Gata6 and Other Cancersmentioning

confidence: 99%

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Sun

Yan

2019

Clinical Genetics

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Cancer is a common type of non-communicable disease, and its morbidity and mortality are rapidly increasing. It is expected to become the largest obstacle to the promotion of global human health in the future. Some transcription factors that play important regulatory roles in embryogenesis and subsequent tissue maintenance can be selectively amplified during tumorigenesis. Due to its high expression in the embryonic endoderm and mesoderm, GATA6 plays a crucial role in the normal development of early human heart, lung, digestive system, adrenal glands, breasts, ovaries, retina, skin, and nervous system. Up to now, overexpression of the GATA6 gene has been shown to play an important role in several cancers, including lung cancer, digestive system tumors, breast cancer, and ovarian cancer. However, the human body is a complex organism, which causes the transcription factor GATA6 to have multiple roles in cancer. In this review, we summarize the multiple roles of transcription factor GATA6 in various cancers and its regulatory mechanisms. The aim is to better understand the relationship between GATA6 gene expression and cancer development and to provide new insights for exploring potential therapeutic targets.

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“…miRNAs are a class of small non-coding RNAs that have vital roles in the regulation of target genes (7). miRNAs are involved in numerous physiological and pathological processes, including tumor development and exacerbation; aberrant miRNA expression has been observed in various types of cancer, including RB (6,8,9).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation

Huang

Nie

et al. 2018

Int J Oncol

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Retinoblastoma (RB) is a well-vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)-182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol-3-OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR-182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR-182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI-Rb-1 RB cells were transfected with a miR-182 mimic or miR-182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR-182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR-182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR-182 on tumor growth and angiogenesis. The results indicated that miR-182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR-182. When the expression of miR-182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway-associated genes were increased in response to miR-182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR-182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.

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Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6

Cited by 40 publications

References 32 publications

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation

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