miR‐30c‐1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor <scp>HMBOX</scp>1

Gong, Jiuyu; Liu, Rongrong; Zhuang, Ran; Zhang, Yun; Fang, Liang; Xu, Zhuwei; Jin, Liang; Wang, Tao; Song, Chaojun; Yang, Kun; Wei, Yuying; Yang, An‐Gang; Jin, Boquan; Chen, Lihua

doi:10.1111/j.1349-7006.2012.02207.x

Cited by 48 publications

(29 citation statements)

References 39 publications

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“…(17,18) miR-30c can also trigger upregulation of transmembrane tumor necrosis factor-a expression and enhance NK cell cytotoxicity against hepatoma cell lines. (19) Recently, there were several targets of miR-30c that were closely related to its tumor suppressor roles in cancer. For instance, miR-30c negatively regulates MTA1 in endometrial cancer cells and downregulates the oncogene BCL9 in ovarian cancer cells.…”

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confidence: 99%

Hypoxia‐induced downregulation of miR‐30c promotes epithelial‐mesenchymal transition in human renal cell carcinoma

et al. 2013

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MicroRNAs (miRNAs), which negatively regulate protein expression by binding protein-coding mRNAs, have been integrated into cancer development and progression as either oncogenes or tumor suppressor genes. miR-30c was reported to be downregulated in several types of cancer. However, its role in human renal cell carcinoma (RCC) remains largely unknown. Here, we show that miR-30c is significantly downregulated in human RCC tissues and cell lines. We found that miR-30c downregulation could be induced by hypoxia in RCC cells in a hypoxia-inducible factors (HIFs) dependent manner. Repression of miR-30c through its inhibitor resulted in reduction of E-cadherin production and promotion of epithelial-mesenchymal transition (EMT), while overexpression of miR-30c inhibited EMT in RCC cells. We identified Slug as a direct target of miR-30c in RCC cells. Slug was upregulated in RCC tissues and its expression could be induced by hypoxia, which is consistent with downregulation of miR-30c by hypoxia. Forced overexpression of Slug in 786-O cells reduced E-cadherin production, and promoted EMT as well as cell migration. Moreover, Slug overexpression abrogated the inhibitory role of miR-30c in regulating EMT and cell migration, indicating miR-30c regulates EMT through Slug in RCC cells. Our findings propose a model that hypoxia induces EMT in RCC cells through downregulation of miR-30c, which leads to subsequent increase of Slug expression and repression of E-cadherin production, and suggest a potential application of miR-30c in RCC treatment. (Cancer Sci 2013; 104: 1609-1617 R enal cell carcinoma (RCC), the most common type of kidney cancer, is one of the leading causes of cancer deaths in western countries, and the overall incidence of RCC is steadily increasing.(1) Despite more than 50% of renal tumors being detected incidentally due to advances in diagnosis, especially improved imaging techniques, about 20-30% of all patients are diagnosed with metastatic disease. In addition, another 20% of patients undergoing nephrectomy will develop metastatic RCC during follow-up. For patients with metastatic RCC, the prognosis is extremely poor, despite multimodal treatment.(2) Therefore, a major challenge for improving clinical outcomes is to understand molecular mechanisms of RCC in detail and search for molecular therapeutic targets.MicroRNAs (miRNAs) are small non-coding RNAs in the size range of 19-25 nucleotides that are cleaved from hairpin pre-miRNA precursors. By binding to imperfect complementary sequences in the 3′-untranslated region (3′UTR) of target mRNAs, miRNAs cause translational repression or mRNA degradation. miRNAs play critical roles in a wide variety of biological process including cell differentiation, proliferation, apoptosis and metabolism. (3,4) Notably, dysregulation of miRNAs has been extensively implicated in cancer pathogenesis in various tumor types.(5) They can act as potential oncogenes or tumor suppressor genes during cancer initiation and progression.(6,7) Accumulating evidence shows that miRNAs play r...

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Hypoxia‐induced downregulation of miR‐30c promotes epithelial‐mesenchymal transition in human renal cell carcinoma

et al. 2013

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“…7,15 Finally, miR-30c-1-3p enhances NK cell cytotoxicity by targeting HMBOX1, an inhibitory transcription factor for cytokines. 16 In summary, miRNAs can modulate both the development and function of NK cells.…”

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confidence: 99%

miR-146a negatively regulates NK cell functions via STAT1 signaling

Han

Hou

et al. 2016

Cell Mol Immunol

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It is known that natural killer (NK) cell function is downregulated in chronic hepatitis B (CHB)-infected patients and in hepatic carcinoma (HCC) patients, but the mechanisms underlying this functional downregulation are largely unclear. In this study, microRNA (miR)-146a expression increased in NK cells from CHB and HCC patients compared with NK cells from healthy donors, and miR-146a levels were negatively correlated to NK cell functions. Overexpression of miR-146a reduced NK cell-mediated cytotoxicity and the production of interferon (IFN)-γ and tumor necrosis factor-α, which were reversed upon inhibition of miR-146a. In NK cells, miR-146a expression was induced by interleukin (IL)-10 and transforming growth factor-β, but reduced after treatment with interleukin-12, IFN-α and IFN-β. We further revealed that miR-146a regulated NK cell functions by targeting STAT1. Taken together, upregulated miR-146a expression, at least partially, attributes to NK cell dysfunction in CHB and HCC patients. Therefore, miR-146a may become a therapeutic target with great potential to ameliorate NK cell functions in liver disease.

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“…To date, NK cell effector functions have been linked with to a number of miRNAs, including miR-155[132–134], miR-150 [128,135], miR-181 [127], and miR-29 [136,137], miR-27a-5p [138], miR-30c-3p [139], miR-30e [124], miR-378 [124], miR-132 [140], miR-200a [140], miR-212 [140], miR-15b [141], miR-122 [141], and miR-362-5p [123] (Table 1). The majority of these miRNAs regulate classical effector molecules, including granzyme B and perforin, as well as the prototype NK cell cytokine IFN-γ.…”

Section: Microrna Regulation Of Nk Cell Gene Expression and Translmentioning

confidence: 99%

Transcriptional and post-transcriptional regulation of NK cell development and function

Leong

Wagner

Ireland

et al. 2017

Clinical Immunology

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Natural killer (NK) cells are specialized innate lymphoid cells that survey against viral infections and malignancy. Numerous advances have improved our understanding of the molecular mechanisms that control NK cell development and function over the past decade. These include both studies on the regulatory effects of transcription factors and translational repression via microRNAs. In this review, we summarize our current knowledge of DNA-binding transcription factors that regulate gene expression and thereby orchestrate NK cell development and activation, with an emphasis on recent discoveries. Additionally, we highlight our understanding of how RNA-bindings microRNAs fine tune the NK cell molecular program. We also underscore the large number of open questions in field that are now being addressed using new technological approaches and genetically engineered model organisms. Ultimately, a deeper understanding of the basic molecular biology of NK cells will facilitate new strategies to manipulate NK cells for the treatment of human disease.

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miR‐30c‐1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1

Cited by 48 publications

References 39 publications

Hypoxia‐induced downregulation of miR‐30c promotes epithelial‐mesenchymal transition in human renal cell carcinoma

Hypoxia‐induced downregulation of miR‐30c promotes epithelial‐mesenchymal transition in human renal cell carcinoma

miR-146a negatively regulates NK cell functions via STAT1 signaling

Transcriptional and post-transcriptional regulation of NK cell development and function

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