miR-34: from bench to bedside

Agostini, Massimiliano; Knight, Richard

doi:10.18632/oncotarget.1825

Cited by 234 publications

(222 citation statements)

References 97 publications

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“…This is in accordance with current literature: the miR-34 family (miR-34a, b, and c) is attracting a lot of attention since it has been found to play a key role as a tumor suppressor in several cancers. 29 Indeed, it is a direct target of the tumor-suppressor gene p53 inducing apoptosis, cell cycle arrest, and senescence when upregulated. It also negatively influences the viability of cancer stem cells and inhibits metastasis formation.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the miR-34 family members bind to the 3ʹ-UTRs of genes such as CDK4 and CDK6 (cell cycle proteins), Bcl-2 (an apoptosis regulator), SNAIL (epithelial-mesenchymal transition) and CD44 (migration and metastasis), thus repressing their expression. 29 Numerous studies have shown the dysregulation of miR-34 in various types of cancers, including hepatocellular, mesothelial and colon cancer, melanomas, leukemia, nasopharyngeal cancer, 30 prostate cancer, 31 neuroblastomas, 32 glioblastoma 33 and breast cancer. 34 Yet, little research has been conducted in EC, apart from a functional study by Li et al 35 demonstrating that miR-34c acts as a tumor suppressor in HEC-1-B cells, and that E2F3 protein may be a target of miR-34c.…”

Section: Discussionmentioning

confidence: 99%

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Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

et al. 2016

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Conventional methods used for histologic classification and grading of endometrial cancer (EC) are not sufficient to predict lymph node metastases. microRNA signatures have recently been related to EC pathologic characteristics or prognosis. The aim of this study was to evaluate whether microRNA profiles of grade 1-2 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. microRNA expression was assessed in nine formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 27 FFPE EC primary tumors with negative lymph node, matched for grade, stage, and lymphovascular space involvement status. A microarray analysis showed that there was more than a twofold significant difference in the expression of 12 microRNAs between the two groups. A quantitative reverse transcriptase-PCR assay was used to confirm these results: the expression levels of five microRNAs (microRNA-34c-5p, -375, -184, -34c-3p, and -34b-5p) were significantly lower in the EC primary tumor with positive lymph node compared with those with negative lymph node. A minimal P-value approach revealed that women with a microRNA-375-fold change o 0.30 were more likely to have positive lymph node (n = 8; 53.3%) compared with those with a microRNA-375-fold change 40.30 (n = 1; 4.8%), P = 0.001. Furthermore, women with a microRNA 184-fold change o0.30 were more likely to have positive lymph node (n = 6; 60.0%) compared with those with a microRNA 184-fold change 40.30 (n = 3; 11.5%), P = 0.006. This is the first study investigating the relative expression of mature microRNA genes in early-stage grade 1-2 EC primary tumors according to the nodal status. This microRNA expression profile provides a potential basis for further study of the microRNA function in EC and could be used as a diagnostic tool for nodal status.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

et al. 2016

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“…More impressively, MRX34, a liposome-based miR-34 mimetic developed by Mirna Therapeutics, has entered the phase of clinical trials for treating patients with liver cancer. The tumor suppressor miR-34a down regulates a number of key oncogenes, including MET, MEK1, CDK4/6, NOTCH, CD44, and immune evasion gene PDL1 [87]. The update on clinical trial with MRX34 American Society of Clinical Oncology (ASCO) Annual meeting 2016 reported that MRX34 has a manageable toxicity profile and evidence of activity in liver cancer, renal cell carcinoma, and melanoma during the phase I study (Hong et al oral presentation at ASCO annual meeting 2016, abstract # 2508).…”

Section: Potential Use Of Microrna For Cancer Therapeuticsmentioning

confidence: 99%

Non-coding RNAs: the cancer genome dark matter that matters!

Ling¹,

Girnita

Buda

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Protein-coding genes comprise only 3% of the human genome, while the genes that are transcribed into RNAs but do not code for proteins occupy majority of the genome. Once considered as biological darker matter, non-coding RNAs are now being recognized as critical regulators in cancer genome. Among the many types of non-coding RNAs, microRNAs approximately 20 nucleotides in length are best characterized and their mechanisms of action are well generalized. microRNA exerts oncogenic or tumor suppressor function by regulation of protein-coding genes via sequence complementarity. The expression of microRNA is aberrantly regulated in all cancer types, and both academia and biotech companies have been keenly pursuing the potential of microRNA as cancer biomarker for early detection, prognosis, and therapeutic response. The key involvement of microRNAs in cancer also prompted interest on exploration of therapeutic values of microRNAs as anticancer drugs and drug targets. MRX34, a liposome-formulated miRNA-34 mimic, developed by Mirna Therapeutics, becomes the first microRNA therapeutic entering clinical trial for the treatment of hepatocellular carcinoma, renal cell carcinoma, and melanoma. In this review, we presented a general overview of microRNAs in cancer biology, the potential of microRNAs as cancer biomarkers and therapeutic targets, and associated challenges.

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“…Studies have shown that miR-34 family members regulate cell proliferation, cell migration, and apoptosis by functioning downstream of p53 signaling (Wang et al, 2013;Agostini and Knight, 2014). For example, miR-34c is functionally required for spermatogenesis (Massimiliano et al, 2011;Liu et al, 2012), whereas miR-34a is involved in neuronal development.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Discovery of two novel miRNAs from the Ovis aries by a combinatorial approach of experiments and bioinformatics

Chang

Wang

Zhang

et al. 2017

IJAR

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In the study, we successful constructed a library from the ovine testis using next-generation sequencing technology, and identified 219 novel miRNAs by bioinformatics. Two of the novel miRNAs (ovis_aries_testis-m0052_5p a nd ovis_aries_testis-m0165_5p), which were expressed in the sheep testis and ovary, and were confirmed by real-time PCR and northern blotting. Ovis_aries_testis-m0052_5p was 23 nucleotides in length, was located on chromosome 15, and had 100% similarity to mmu-miR-34c-5p, hsa-miR-34c-5p, gga-miR-34c-5p, and cfa-miR-34c. Ovis_aries_testis-m0165_5p was 21 nucleotides in length, located on chromosome 5, and had 100% similarity to mmu-miR-145a-5p, hsa-miR-145-5p, ssc-miR-145-5p, and bta-miR-145. The pre-miRNAs for Ovis_aries_testis-m0052_5p and Ovis_aries_testis-m0165_5p were 75 and 81 nucleotides in length, and both had a standard hairpin stem-loop structure. From the consistency of the sequence and structure, we speculated that ovis_aries_testis-m0052_5p had a function similar to hsa-miR-34c-5p, mmumiR-34c-5p, and ovis_aries_testis-m0165_5p had a function similar to hsa-miR-145-5p, which were involved in the fine regulation of cell survival, spermatozoon generate, breeding activities. Therefore, we defined the identified miRNAs as oar-miR-34c-5p and oar-miR-145-5p. The results will enrich the miRNA database, and provide the basis for research into the regulatory mechanisms of miRNA in relation to breeding activities.

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miR-34: from bench to bedside

Cited by 234 publications

References 97 publications

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Non-coding RNAs: the cancer genome dark matter that matters!

Discovery of two novel miRNAs from the Ovis aries by a combinatorial approach of experiments and bioinformatics

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