Updates and current challenges in microRNA research for personalized medicine in ovarian cancer

Mandilaras, Victoria; Vernon, Megane; Meryet‐Figuiere, Matthieu; Karakasis, Katherine; Lambert, Bernard; Poulain, Laurent; Oza, Amit M.; Denoyelle, Christophe; Lheureux, Stéphanie

doi:10.1080/14712598.2017.1340935

Cited by 18 publications

(21 citation statements)

References 116 publications

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“…9 Recent studies demonstrated that the dysregulation of miRNAs significantly contributes to the development and progression of ovarian cancer. [10][11][12] For example, Zhou et al found that miR-183 modulated the proliferation and apoptosis of ovarian cancer cells via targeting the TGFβ/Smad4 pathway. 13 Overexpression of miR-598 inhibited the growth and metastasis of ovarian cancer cells by regulating the expression of URI.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Shi¹,

Yang²,

Zhang³

et al. 2019

OTT

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Background: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized. Materials and methods: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3ʹ-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis. Results: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3ʹ-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells. Conclusion: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Shi¹,

Yang²,

Zhang³

et al. 2019

OTT

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“…Specific miRNA readouts could assist clinicians in identifying the most effective endometriosis therapy for each individual and provide a way to track whether the disease recurs. The use of noncoding RNAs as diagnostic and prognostic biomarkers is promising in ovarian cancer [132] and colorectal cancer [133], as a strategy for patient stratification in clinical trials and predicting therapeutic response. When the first-line therapies, including NSAIDs and oral contraceptives, are not effective, a patient's unique miRNA expression pattern may help guide the decision of when to move on to second-line therapy (estrogen-suppressing drugs), or even to predict early on how effective a certain therapy may be.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in endometriosis: biological function and emerging biomarker candidates†

Björkman

Taylor

2019

Biology of Reproduction

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MicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.

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“…MicroRNA is a promising therapeutic agent against many diseases, including cancer . However, several challenges limit miRNA‐based clinical applications, including effective delivery of therapeutic miRNA, lack of specificity and induction of the immune response . Gap junctions are selectively permeable, which allows for the exchange of secondary messenger molecules and metabolites between the cytoplasm and the extracellular environment .…”

Section: Discussionmentioning

confidence: 99%

“…4,9,39,40 However, several challenges limit miRNA-based clinical applications, including effective delivery of therapeutic miRNA, lack of specificity and induction of the immune response. [41][42][43] Gap junctions are selectively permeable, which allows for the exchange of secondary messenger molecules and metabolites between the cytoplasm and the extracellular environment. 16 Notably, transmission of miRNAs through gap junctions is efficient and specific…”

Section: Discussionmentioning

confidence: 99%

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

et al. 2019

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Micro RNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of micro RNA , which exerts biological effects on tumor cells. However, the length of micro RNA that can pass through certain gap junctions composed of specific connexin remains unknown. To address this question, the present study investigated the permeability of gap junctions composed of various connexins, including connexin 43, connexin 32 or connexin 37, to micro RNA s consisting of 18‐27 nucleotides in glioma cells and cervical cancer cells. Results indicated that all of the micro RNA s were able to be transferred from donor glioma cells to neighboring cells through the connexin 43 composed gap junction, but not the gap junctions composed of connexin 32 or connexin 37, in cervical cancer cells. Downregulation of the function of gap junctions comprising connexin 43 by pharmacological inhibition and sh RNA significantly decreased the transfer of these micro RNA s. In contrast, gap junction enhancers and overexpression of connexin 43 effectively increased these transfers. In glioma cells, cell proliferation was inhibited by micro RNA ‐34a. Additionally, these effects of micro RNA ‐34a were significantly enhanced by overexpression of connexin 43 in U251 cells, indicating that gap junctions play an important role in the antitumor effect of micro RNA by transfer of micro RNA to neighboring cells. Our data are the first to clarify the pattern of micro RNA transmission through gap junctions and provide novel insights to show that antitumor micro RNA s should be combined with connexin 43 or a connexin 43 enhancer, not connexin 32 or connexin 37, in order to improve the therapeutic effect.

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Updates and current challenges in microRNA research for personalized medicine in ovarian cancer

Cited by 18 publications

References 116 publications

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

MicroRNAs in endometriosis: biological function and emerging biomarker candidates†

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

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