miR-30c-2-3p and miR-30a-3p: New Pieces of the Jigsaw Puzzle in HIF2α Regulation

Moch, Holger; Lukamowicz-Rajska, Magdalena

doi:10.1158/2159-8290.cd-13-0897

Cited by 14 publications

(7 citation statements)

References 10 publications

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“…We also showed that miR-196a-5p is up-regulated in LNM containing at least 70 % of tumor cells. In other cancers, miR-196a-5p and miR-30c-2-3p have also been respectively identified as up- [ 61 – 63 ] and down- [ 64 , 65 ] regulated during migration and invasion. So, although the microRNA expression profiles of primary tumors of PTC and LNM are very similar, some microRNAs are modulated and could participate to metastasis formation.…”

Section: Discussionmentioning

confidence: 99%

New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer

et al. 2015

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BackgroundPapillary Thyroid Cancer (PTC) is the most prevalent type of endocrine cancer. Its incidence has rapidly increased in recent decades but little is known regarding its complete microRNA transcriptome (miRNome). In addition, there is a need for molecular biomarkers allowing improved PTC diagnosis.MethodsWe performed small RNA deep-sequencing of 3 PTC, their matching normal tissues and lymph node metastases (LNM). We designed a new bioinformatics framework to handle each aspect of the miRNome: whole expression profiles, isomiRs distribution, non-templated additions distributions, RNA-editing or mutation. Results were validated experimentally by qRT-PCR on normal samples, tumors and LNM from 14 independent patients and in silico using the dataset from The Cancer Genome Atlas (small RNA deepsequencing of 59 normal samples, 495 PTC, and 8 LNM).ResultsWe performed small RNA deep-sequencing of 3 PTC, their matching normal tissues and lymph node metastases (LNM). We designed a new bioinformatics framework to handle each aspect of the miRNome: whole expression profiles, isomiRs distribution, non-templated additions distributions, RNA-editing or mutation. Results were validated experimentally by qRT-PCR on normal samples, tumors and LNM from 14 independent patients and in silico using the dataset from The Cancer Genome Atlas (small RNA deep-sequencing of 59 normal samples, 495 PTC, and 8 LNM). We confirmed already described up-regulations of microRNAs in PTC, such as miR-146b-5p or miR-222-3p, but we also identified down-regulated microRNAs, such as miR-7-5p or miR-30c-2-3p. We showed that these down-regulations are linked to the tumorigenesis process of thyrocytes. We selected the 14 most down-regulated microRNAs in PTC and we showed that they are potential biomarkers of PTC samples. Nevertheless, they can distinguish histological classical variants and follicular variants of PTC in the TCGA dataset. In addition, 12 of the 14 down-regulated microRNAs are significantly less expressed in aggressive PTC compared to non-aggressive PTC. We showed that the associated aggressive expression profile is mainly due to the presence of the BRAF V600E mutation. In general, primary tumors and LNM presented similar microRNA expression profiles but specific variations like the down-regulation of miR-7-2-3p and miR-30c-2-3p in LNM were observed. Investigations of the 5p-to-3p arm expression ratios, non-templated additions or isomiRs distributions revealed no major implication in PTC tumorigenesis process or LNM appearance.ConclusionsOur results showed that down-regulated microRNAs can be used as new potential common biomarkers of PTC and to distinguish main subtypes of PTC. MicroRNA expressions can be linked to the development of LNM of PTC. The bioinformatics framework that we have developed can be used as a starting point for the global analysis of any microRNA deep-sequencing data in an unbiased way.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2082-3) contains supplementary materia...

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Section: Discussionmentioning

confidence: 99%

New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer

et al. 2015

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“…Stabilization of HIF-1 and −2 through the loss of VHL is not the only factor contributing to the high levels of these transcription factors in RCC. Mathew et al have shown that RCC have low levels of the microRNAs miR-30-2-3p and miR-30a-3p compared to the normal renal parenchyma [31,32]. These microRNAs interfere with the translation of the HIF mRNAs and their absence from RCC cells allows for the HIF transcripts to be efficiently translated.…”

Section: Rcc Microvasculaturementioning

confidence: 99%

The tumor microenvironment in renal cell cancer

Mier

2019

Current Opinion in Oncology

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Purpose of review: In addition to the provision of nutrients and growth factors that facilitate tumor cell proliferation and metastasis, the tumor microenvironment (MEV) restricts immune surveillance of tumor-associated antigens and limits the efficacy of immune checkpoint inhibitors (ICIs), tumor vaccines, and other immune therapies. This review will focus on the immunosuppressive mechanisms operative within the tumor MVE of renal cell carcinoma (RCC). Recent findings: Several of the immunosuppressive mechanisms within the tumor MEV have been identified and are potentially druggable. Clinical trials with agents that target several of these inhibitory pathways are currently underway. Summary: Although RCC is one of several tumor types responsive to ICIs, the effectiveness of these agents is likely to be limited by the various tumor-infiltrating bone marrow-derived myeloid cells that comprise the MEV. Several strategies to combat the recruitment of these cells into tumor tissue or to neutralize their immunosuppressive function have shown encouraging results in animal tumor models and clinical trials. Keywords microenvironment (MEV); renal cell carcinoma (RCC); myeloid-derived suppressor cells (MDSC); tumor-associated macrophages (TAM); microvasculature; tumor-infiltrating lymphocytes (TIL); cytotoxic T lymphocytes (CTL); regulatory T cells (Tregs); immune checkpoint inhibitor (ICI); vascular endothelial growth factor (VEGF); hypoxia-inducible factor (HIF); arginase; indoleamine dioxygenase (IDO) Conflicts of interest There are no conflicts of interest.

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“…and HIF-2α can regulate miR-30a-3p expression negatively [29]. Then, we found loss of miR-30a-3p contributed to the progression of neuropathic pain.…”

Section: Discussionmentioning

confidence: 74%

“…In a mouse model of traumatic peripheral nerve injury, a persistent intimal hypoxia can cause neuralgia with elevated levels of HIF-1α [ 28 ]. HIF-1α and HIF-2α can regulate miR-30a-3p expression negatively [ 29 ]. Then, we found loss of miR-30a-3p contributed to the progression of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic modification of BDNF mediates neuropathic pain via miR-30a-3p/EP300 axis in CCI rats

2020

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Recent investigation of microRNAs on chronic pain has developed a breakthrough in neuropathic pain management. In this study, decreased expression of miR-30a-3p was reported using qRT-PCR analysis and loss of miR-30a-3p promoted neuropathic pain progression in sciatic nerve chronic constrictive injury rats through determining the pain threshold. We predicted miR-30a-3p could target E-cadherin transcriptional activator (EP300) via bioinformatics analysis. Meanwhile, we found that brain-derived neurotrophic factor (BDNF) is involved in neuropathic pain. Here, we exhibited that EP300 epigenetically up-regulated BDNF via enhancing acetylated histone H3 and H4 on the promoter. For another, miR-30a-3p was able to modify the level of BDNF and acetylated histone H3 and H4. Loss of miR-30a-3p enhanced EP300 and BDNF colocalization in CCI rats. Subsequently, it was shown that increased EP300 induced neuropathic pain by an enhancement of neuronal BDNF level in vivo. To sum up, it was revealed that epigenetic modification of BDNF promoted neuropathic pain via EP300 induced by miR-30a-3p in CCI rats.

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miR-30c-2-3p and miR-30a-3p: New Pieces of the Jigsaw Puzzle in HIF2α Regulation

Cited by 14 publications

References 10 publications

New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer

New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer

The tumor microenvironment in renal cell cancer

Epigenetic modification of BDNF mediates neuropathic pain via miR-30a-3p/EP300 axis in CCI rats

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