Biphasic regulation of autophagy by miR-96 in prostate cancer cells under hypoxia

Ma, Yi; Yang, Hao; Dong, Baijun; Zou, Han; Zhou, Yan; Kong, Xian Ming; Huang, Yazhuo

doi:10.18632/oncotarget.2396

Cited by 66 publications

(45 citation statements)

References 49 publications

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“…miR-23a is secreted by hypoxic lung cancer cells and transferred to endothelial cells via exosome secretion To identify the exosome-associated small RNAs, we determined the levels of exosomal small RNAs that are induced by hypoxia. [23][24][25][26] Figure 3a and Supplementary Table 2 show that levels of miR-103a, -23a, -370 and -373 increased in CL1-5 cells under hypoxic conditions. Of these, miR-23a levels increased in various lung cancer cell lines, regardless of stage and RAS status (wild type or mutation) (Figure 3a).…”

Section: Resultsmentioning

confidence: 96%

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

et al. 2017

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Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

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Section: Resultsmentioning

confidence: 96%

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

et al. 2017

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“…During the preparation of this manuscript, Ma et al (78) published an article that hypothesized a biphasic regulation of autophagy by miR-96 in prostate cancer cells in hypoxic conditions. These data suggests that there may be an expression level threshold of miR-96 in certain situations, including hypoxia, and on either side of this threshold the miR-96 may have the opposite effect.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells

et al. 2017

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Abstract. MicroRNAs (miRNA/miR) are short non-coding RNAs that function in the endogenous regulation of genes. miRNAs serve important roles in cellular events such as apoptosis, cell proliferation, migration, invasion, autophagy and the cell cycle. They also control the genesis and progression of tumors. Autophagy is a self-digestive process that occurs as a response to stress, and serves two opposite roles in tumor promotion or inhibition that may result in resistance to therapy. A number of studies have revealed that miRNAs control autophagic activity by targeting autophagy-associated genes, particularly in cancer. These previous studies demonstrated that miR-96-5p is upregulated in several types of malignant tumors. However, other functions of miR-96-5p in breast cancer, particularly those that are associated with autophagy, remain unknown. miR-96-5p expression was demonstrated to be upregulated in breast cancer cells compared with in normal breast epithelial cells. The overexpression of miR-96-5p inhibited autophagy, particularly starvation-induced autophagy, in MCF-7 and MDA-MB-231 cells. In addition, this inhibitory effect may have resulted in the suppression of Forkhead box O1. Additionally, the overexpression of miR-96-5p may promote cell proliferation, migration and invasion and inhibit apoptosis in MCF-7 and MDA-MB-231 cells. These data indicate that miR-96-5p is involved in the progression of breast cancer cells and may represent a potential therapeutic target for the treatment of breast cancer.

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“…It is known, that many upstream regulators, including HSF2, β-catenin/TCF/LEF-1, TGF-β, SP1, P53, growth hormones, Akt/FOXP3, and MYOD increase the expression of miR-183-96-182 cluster [3, 7–18], while ZEB1, MYCN, HDAC, EVI1, and KLF-3 repress this cluster [9, 19–22]. Hypoxia and/or starvation are known to up-regulate miR-96/miR-182 expression, and miR-183/miR-182 increases the expression of hypoxia inducible factor 1α (HIF-1α) [23–27]. Thus, the relationship between miR-183-96-182 cluster and hypoxia or starvation still needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

Liang

Fan

et al. 2016

Oncotarget

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Previous studies have reported aberrant expression of the miR-183-96-182 cluster in a variety of tumors, which indicates its' diagnostic or prognostic value. However, a key characteristic of the miR-183-96-182 cluster is its varied expression levels, and pleomorphic functional roles in different tumors or under different conditions. In most tumor types, the cluster is highly expressed and promotes tumorigenesis, cancer progression and metastasis; yet tumor suppressive effects have also been reported in some tumors. In the present study, we discuss the upstream regulators and the downstream target genes of miR-183-96-182 cluster, and highlight the dysregulation and functional roles of this cluster in various tumor cells. Newer insights summarized in this review will help readers understand the different facets of the miR-183-96-182 cluster in cancer development and progression.

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Biphasic regulation of autophagy by miR-96 in prostate cancer cells under hypoxia

Cited by 66 publications

References 49 publications

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1

Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

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