Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro

Yang, Wei; Sun, Ting; Cao, Jianping; Liu, Fenju; Tian, Ye; Zhu, Wei

doi:10.1016/j.yexcr.2012.02.010

Cited by 111 publications

(89 citation statements)

References 34 publications

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“…This may be exploited to sensitize these tumors to agents targeting the miR-210 pathway that the tumors may depend on. In support of this concept, it has been shown that targeting miR-210 sensitizes tumor cells to radiation in a variety of cancers [125,182,183], inhibits the migration and invasion of renal cell carcinoma cells [96], and leads to enhanced cell death [123]. Thus, we speculate that targeting miR-210 would compromise the 'fitness' of tumor cells with high-level miR-210 expression, especially those residing in a severely hypoxic microenvironment that is distant from tumor vasculature.…”

Section: Mir-210 As a Potential Cancer Therapeutic Targetmentioning

confidence: 60%

“…Thus, it is not surprising that miR-210, the most consistently induced miRNA in hypoxic microenvironments, is implicated in regulating this critical process. Most of the evidence supports an anti-apoptotic property of miR-210: expression of miR-210 can protect cells from apoptosis [66,75,160,161], while downregulation of miR-210 leads to apoptosis [66,68,[123][124][125]162].…”

Section: Mir-210 Regulates Angiogenesismentioning

confidence: 99%

“…These include E2F3 [162], Ptp1b [126], caspase-8-associated protein-2 (CASP8AP2) [75], and apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) [125]. However, among all these targets, only CASP8AP2 has been verified in independent studies [163].…”

Section: Mir-210 Regulates Angiogenesismentioning

confidence: 99%

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Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response

Huang

Zuo

2014

ABBS

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Hypoxia is a key component of the tumor microenvironment and represents a well-documented source of therapeutic failure in clinical oncology. Recent work has provided support for the idea that non-coding RNAs, and in particular, microRNAs, may play important roles in the adaptive response to low oxygen in tumors. Specifically, all published studies agree that the induction of microRNA-210 (miR-210) is a consistent feature of the hypoxic response in both normal and malignant cells. miR-210 is a robust target of hypoxia-inducible factors, and its overexpression has been detected in a variety of diseases with a hypoxic component, including most solid tumors. High levels of miR-210 have been linked to an in vivo hypoxic signature and to adverse prognosis in breast and pancreatic cancer patients. A wide variety of miR-210 targets have been identified, pointing to roles in mitochondrial metabolism, angiogenesis, DNA damage response, apoptosis, and cell survival. Such targets are suspected to affect the development of tumors in multiple ways; therefore, an increased knowledge about miR-210's functions may lead to novel diagnostic and therapeutic approaches in cancer.

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Section: Mir-210 As a Potential Cancer Therapeutic Targetmentioning

confidence: 60%

Section: Mir-210 Regulates Angiogenesismentioning

confidence: 99%

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Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response

Huang

Zuo

2014

ABBS

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“…34 In a recent study using synthetically designed miRNA-mowers, researchers proved the ability of the miR-183-96-182 cluster and miR-210 to reduce cell proliferation, to activate the apoptotic machinery, and to inhibit migration. 35 Knockdown of the miR-183/96/182 cluster targeted the PI3K/AKT/mTOR pathway and subsequently enhanced apoptosis. miR-210 is recognized as a novel biomarker for hypoxia, but an in vitro study using anti-miR-210 suggested it was connected with reduced proliferation and with migration and an activation of apoptosis.…”

Section: -9mentioning

confidence: 99%

Clinical and pathological implications of miRNA in bladder cancer

Braicu¹,

Cojocneanu²,

Chira³

et al. 2015

IJN

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MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.

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“…In particular, radiotherapy could benefit from an in-depth knowledge of miR-210 status. Thus, miR-210 overexpression has been shown to increase radioresistance in human lung cancer cell lines (64), while its down-regulation enhances radiosensitivity in hypoxic human hepatoma cells in vitro (182), and, most recently, in vivo (184). These findings have not yet been translated in humans in vivo but intriguingly, in a series of head and neck patients treated with post-operative radiotherapy, the expression of miR-210 was highly prognostic, suggesting that miR-210 may be a marker of radiotherapy resistance (54).…”

Section: Mir-210: Candidate Cancer Biomarkermentioning

confidence: 99%

HypoxamiRs and Cancer: From Biology to Targeted Therapy

Gee

Ivan

Calin

et al. 2014

Antioxidants & Redox Signaling

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Significance: Hypoxia is a hallmark of the tumor microenvironment and represents a major source of failure in cancer therapy. Recent Advances: Recent work has generated extensive evidence that microRNAs (miRNAs) are significant components of the adaptive response to low oxygen in tumors. Induction of specific miRNAs, collectively termed hypoxamiRs, has become an accepted feature of the hypoxic response in normal and transformed cells. Critical Issues: Overexpression of miR-210, the prototypical hypoxamiR, is detected in most solid tumors, and it has been linked to adverse prognosis in many tumor types. Several miR-210 target genes, including iron-sulfur (Fe-S) cluster scaffold protein (ISCU) and glycerol-3-phosphate dehydrogenase 1-like (GPD1L), have been correlated with prognosis in an inverse fashion to miR-210, suggesting that their downregulation by miR-210 occurs in vivo and contributes to tumor growth. Additional miRNAs are modulated by decreased oxygen tension in a more tissue-specific fashion, adding another level of complexity over the classic hypoxia-regulated gene network. Future Directions: From a biological standpoint, hypoxamiRs are emerging modifiers of cancer cell response to the adaptive challenges of the microenvironment. From a clinical perspective, assessing the status of these miRNAs may contribute to a detailed understanding of hypoxia-induced mechanisms of resistance and/or to the fine-tuning of future hypoxia-modifying therapies. Antioxid. Redox Signal. 21, 1220-1238.

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Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro

Cited by 111 publications

References 34 publications

Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response

Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response

Clinical and pathological implications of miRNA in bladder cancer

HypoxamiRs and Cancer: From Biology to Targeted Therapy

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