MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling

Chang, Ruimin; Xu, Jiangfeng; Fěng, Fang; Yang, Hao; Yang, Lian-Yue

doi:10.1007/s13277-016-4919-z

Cited by 54 publications

(42 citation statements)

References 36 publications

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“…The results suggested an association between miR-320 and HIF-1α in adjusting RB progression. Increasing evidence has shown that miRNA interfere with the metastasis and invasion of various types of cancer via the regulation of HIF-1α (21)(22)(23)(24). In this study, a luciferase reporter assay was employed to investigate the effect of miR-320 on HIF-1α.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Liang¹,

Chen²,

Zhu³

2017

Experimental and Therapeutic Medicine

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Abstract. Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells. The results demonstrated that HIF-1α was the downstream target of miR-320, and decreased miRNA-320 or HIF-1α lead to the inhibition of autophagy in WERI-RB1 cells. Compared with WERI-RB1 cells that were not transfected, silenced HIF-1α caused a 1.41-fold increase (P<0.01) in p62, a 2.71-fold decrease of Beclin1, and inhibited miRNA-320. Silenced HIF-1α also resulted in 7.29-and 7.43-fold increases in phosphorylated-mechanistic target of rapamycin (mTOR) and mTOR, respectively. In conclusion, the present results suggest that miRNA-320 may regulate the development of autophagy by targeting HIF-1α and autophagy-related proteins in RB under hypoxic conditions.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Liang¹,

Chen²,

Zhu³

2017

Experimental and Therapeutic Medicine

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“…Several studies have demonstrated that EWS-FLI1 is capable of modulating miRNA expression; however, miR-130b expression was not shown to be altered in these studies 48,49 . While miR-130b has been independently shown to contribute to metastatic properties in other malignancies, we cannot exclude the contribution of the fusion transcript to aid in metastatic potential dictated by miR-130b 7,50 . Overall, we highlight this as a potential mechanism to promote metastasis in Ewing sarcoma, but cannot exclude other mechanisms of action such as input from other GTPases or components of the MAPK pathway.…”

Section: Discussionmentioning

confidence: 92%

“…48,49 While miR-130b has been independently shown to contribute to metastatic properties in other malignancies, we cannot exclude the contribution of the fusion transcript to aid in metastatic potential dictated by miR-130b. 7,50 Overall, we highlight this as a potential mechanism to promote metastasis in ES, but cannot exclude other mechanisms of action such as input from other GTPases or components of the MAPK pathway. Future and ongoing studies include testing of relevant inhibitors of the MAPK and JNK as well as PAK1 in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 94%

“…Although miRNAs are critical for normal cellular homeostasis, a vast amount of miRNA research demonstrates that miRNAs are often aberrantly expressed in various neoplasms and can promote aggressive, metastatic disease 4–6 . Accumulating evidence suggests miR-130b is overexpressed in a number of malignancies and therefore acts as an oncomiR in these tumors 7–9 . It has been shown that overexpression of miR-130b increases stemness and chemoresistance in glioblastoma and increases cell migration and invasion in glioma 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] Accumulating evidence suggests miR-130b is overexpressed in a number of malignancies and therefore acts as an oncomiR in these tumors. [7][8][9] It has been shown that overexpression of miR-130b increases stemness and chemoresistance in glioblastoma and increases cell migration and invasion in glioma. 10,11 Furthermore, miR-130b was identified as oncogenic miR and is part of pan-cancer oncogenic superfamily that targets key pathways often deregulated in cancer including p53 and TGFb.…”

Section: Introductionmentioning

confidence: 99%

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miR‐130b directly targets ARHGAP1 to drive activation of a metastatic CDC42‐PAK1‐AP1 positive feedback loop in Ewing sarcoma

Satterfield

Shuck

Kurenbekova

et al. 2017

Intl Journal of Cancer

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Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing towards sarcoma metastasis. Specifically, we demonstrated miR-130b induces proliferation, invasion, and migration in vitro and increased metastatic potential in vivo. Using microarray analysis of ES cells with differential miR-130b expression we identified alterations in downstream signaling cascades including activation of the CDC42 pathway. We identified Arhgap1, which is a negative regulator of CDC42, as a novel, direct target of miR-130b. In turn, downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to an upstream consensus binding site within the miR-130b promoter. Finally, small molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP-1 target genes, including primary miR-130b transcripts, and mir-130b oncogenic properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken together, our findings identify and characterize a novel, targetable miR-130b regulatory network that promotes ES metastasis.

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Circulating miR‐130b‐ and miR‐21‐based diagnostic markers and therapeutic targets for hepatocellular carcinoma

Zhang

Qiang

et al. 2019

Molec Gen & Gen Med

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BackgroundHepatocellular carcinoma (HCC) is one of the histological types of primary liver cancer with high recurrence and mortality in the world. The purpose of this study was to explore the diagnostic and therapeutic value for HCC patients.MethodsIn this study, we investigated the circulating miR‐130b‐5p (miR‐130b) and miR‐21‐5p (miR‐21) expression levels in patients with HCC and their association with clinical parameters.ResultsThe circulating miR‐130b and miR‐21 were all upregulated in patients with HCC. The upregulated microRNAs (miRNAs) were associated with clinicopathological parameters of tumor capsular infiltration and clinical TNM stage. Also, the poor prognosis of patients with upregulated miRNAs levels suggested that it may be an effective therapeutic target for HCC by suppression of the miRNAs levels. In addition, the combined detection of serum miR‐130b and miR‐21 performed better in the diagnosis of HCC with a sensitivity of 92.16% and an accuracy rate of 77.51%. In vivo, tumors treated with the nanoparticle (NP)/miR‐130b and miR‐21 inhibitor complexes had significantly lower growth than the other groups.ConclusionThe circulating miR‐130b and miR‐21 can be used as potential tumor biomarkers to diagnose liver cancer, and the combined detection of serum miR‐130b and miR‐21 is superior to the diagnosis of HCC. NP/miR‐130b and miR‐21 inhibitor complexes show good therapeutic effects in vivo and are expected to become therapeutic targets worthy of further study.

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MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling

Cited by 54 publications

References 36 publications

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

miR‐130b directly targets ARHGAP1 to drive activation of a metastatic CDC42‐PAK1‐AP1 positive feedback loop in Ewing sarcoma

Circulating miR‐130b‐ and miR‐21‐based diagnostic markers and therapeutic targets for hepatocellular carcinoma

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