MicroRNA Interactome Multiomics Characterization for Cancer Research and Personalized Medicine: An Expert Review

Sindhu, K J; Venkatesan, Narayanan; Karunagaran, Devarajan

doi:10.1089/omi.2021.0087

Cited by 6 publications

(7 citation statements)

References 127 publications

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“…Various experimental strategies have been employed to examine different aspects of the miRNA regulatory process (Figure 4 ). First information on the miRNA-mRNA target interplay can be gained by approaches that integrate cellular expression data of miRNAs and their predicted targets ( 131 , 143 , 144 ). Conclusive experimental data are obtained from comparisons between healthy and diseased cells or as the result of an experimentally altered miRNA expression.…”

Section: Introductionmentioning

confidence: 99%

The miRNA–target interactions: An underestimated intricacy

Diener,

Keller,

Meese

2023

Nucleic Acids Research

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MicroRNAs (miRNAs) play indispensable roles in posttranscriptional gene regulation. Their cellular regulatory impact is determined not solely by their sheer number, which likely amounts to >2000 individual miRNAs in human, than by the regulatory effectiveness of single miRNAs. Although, one begins to develop an understanding of the complex mechanisms underlying miRNA–target interactions (MTIs), the overall knowledge of MTI functionality is still rather patchy. In this critical review, we summarize key features of mammalian MTIs. We especially highlight latest insights on (i) the dynamic make-up of miRNA binding sites including non-canonical binding sites, (ii) the cooperativity between miRNA binding sites, (iii) the adaptivity of MTIs through sequence modifications, (iv) the bearing of intra-cellular miRNA localization changes and (v) the role of cell type and cell status specific miRNA interaction partners. The MTI biology is discussed against the background of state-of-the-art approaches with particular emphasis on experimental strategies for evaluating miRNA functionality.

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Section: Introductionmentioning

confidence: 99%

The miRNA–target interactions: An underestimated intricacy

Diener,

Keller,

Meese

2023

Nucleic Acids Research

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“…evidence for miRNA targets can be provided by an inverse relationship between the levels of miRNA expression and those of the target mRNA and/or its encoded target protein in the cells of interest [91,92]. Further confirmation of true miRNA targets can be generated by transfecting miRNAs or inhibitors in cells of interest and measuring the effects both on mRNA targets and on proteins encoded by these mRNAs [86].…”

Section: Open Accessmentioning

confidence: 99%

Emerging concepts of miRNA therapeutics: from cells to clinic

2022

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“…9,10 In particular, miRNAs in sEV circulating in the blood have been shown to be dysregulated in the circulating blood of patients with cancer 11 and are used as noninvasive biomarkers for early diagnosis and evidence of tumor progression in various types of malignancies. [12][13][14] In comparison to exosomes in serum, the molecular composition and functions of sEV in the peritoneal cavity are less understood, presumably due to the difficulty of obtaining samples from patients. However, previous studies have shown that sEV derived from gastric [15][16][17][18] or ovarian 19 cancer cells as well as from malignant ascites from patients 20 are efficiently incorporated in MCs and induces MMT, which facilitates the adhesion of tumor cells to MC and enhances development and growth of PM from gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Emerging evidence suggests that tumor‐secreted EV contains various functional molecules such as proteins, DNA, and various types of RNAs, 6–8 conveying potential biological information to target organs and creating a premetastatic niche to establish organotypic metastases 9,10 . In particular, miRNAs in sEV circulating in the blood have been shown to be dysregulated in the circulating blood of patients with cancer 11 and are used as noninvasive biomarkers for early diagnosis and evidence of tumor progression in various types of malignancies 12–14 …”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer

et al. 2023

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Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR‐29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR‐29b can affect the development of PM in a murine model. UE6E7T‐12, human bone marrow‐derived mesenchymal stem cells (BMSCs), were transfected with miR‐29b‐integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR‐29b compared with negative controls. Treatment with transforming growth factor‐β1 decreased the expression of E‐cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue‐derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR‐29b‐rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC‐4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA‐29b‐rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell‐derived sEV are a useful carrier for IP administration of miR‐29b, which can suppress the development of PM of gastric cancer.

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MicroRNA Interactome Multiomics Characterization for Cancer Research and Personalized Medicine: An Expert Review

Cited by 6 publications

References 127 publications

The miRNA–target interactions: An underestimated intricacy

The miRNA–target interactions: An underestimated intricacy

Emerging concepts of miRNA therapeutics: from cells to clinic

Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer

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