Characterizing isomiR variants within the micro<scp>RNA</scp>‐34/449 family

Mercey, Olivier; Popa, Alexandra; Cavard, Amélie; Paquet, Agnès; Chevalier, B.; Pons, Nicolas; Magnone, Virginie; Zangari, Joséphine; Brest, Patrick; Zaragosi, Laure‐Emmanuelle; Ponzio, Gilles; Lebrigand, Kévin; Barbry, Pascal; Marcet, Brice

doi:10.1002/1873-3468.12595

Cited by 48 publications

(46 citation statements)

References 54 publications

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“…It is known that miRNA genomic clusters are often co-transcribed as related miRNAs, which share the same seed region or belong to functionally related miRNA families. A typical example is given by the miR-34/449 superfamily, which exhibits extensive genomic redundancy by encompassing six homologous miRNAs (miR-34a, miR-34b/c and miR-449a/b/c) located on three distinct genomic loci (28). While the tumor suppressor role of miR-34 has been largely established, the effects of the miR-449 family members have not been addressed in human CRC, as well as CAC (29,30).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Feng

Song

et al. 2018

Oncol Rep

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An early diagnosis of colitis‑associated colorectal cancer (CAC) is important for its clinical management. However, it is currently difficult to distinguish the different stages of CAC development. MicroRNA dysregulation is common in human colorectal disorders, however little is known regarding whether miRNA affects tumor progression by regulating inflammation. In the present study, we identified a novel miRNA (miR‑449a), the expression of which was significantly reduced in CAC tissues than in paired adjacent non‑cancerous tissues (ANTs). Notably, the level of miR‑449a was in a markedly decreased pattern during the neoplastic transformation of ulcerative colitis (UC)‑to‑CAC, as demonstrated by both clinical investigations and the experimental mouse model induced by AOM/DSS treatment. In addition, we observed that decreased miR‑449a expression was associated with advanced T or N status, later clinical stage and poor histological differentiation of CAC. Mechanistic studies revealed that miR‑449a inhibited the growth and metastasis of human colon cancer cells by directly binding to the 3'‑UTR of Notch‑1 and thereby, suppressed the activation of the Notch signaling pathway. Therefore, these findings provide strong evidence for the translational potential of miR‑449a in the discrimination of patients with UC that is likely to progress into CAC, from those unlikely to progress, as well as in the prognosis and diagnosis of CAC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Feng

Song

et al. 2018

Oncol Rep

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“…Moderate level of isomiR expression has been observed between Dicer-independent miRNA and non-dominant miRNA, suggesting complex miRNA maturation process at isomiR level [38]. The study performed by Mercey and colleagues [39] on human miR-34/449 family suggested that isomiR variants which differ by single canonical counterpart can share biological functions indicatind additional mechanism by which regulation of complex biological function can be perfectly and easily employed by miRNA machinery.…”

Section: Importance Of Isomirsmentioning

confidence: 99%

Biogenesis and biological implications of isomiRs in mammals- a review

Dhanoa

Verma

Sethi

et al. 2019

ExRNA

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Background: IsomiRs, the sequence-variants of microRNA (miRNA), are characterized by variation at the 3′-and/or 5′-end(s) of canonical miRNA-sequence as a result of nucleotide addition or deletion or substitution. These sequence alterations could be created either due to imprecise cleavage of miRNA sequence by drosha or dicer enzymes or through the addition of nucleotides at 3′ end during miRNA-biogenesis. Main body: The present review elaborates the biogenesis vis-à-vis role of isomiRs in disease-related traits in human and animals. The differential expression of isomiRs has been detected in the early and late developmental phases during embryogenesis in fruit fly and halibut (Hippoglossus hippoglossus). Multidimentional role of isomiRs viz. in gene regulation, evolution, RNA interference pathway and differentiation of tumorous cells etc. has attracted researchers to explore the biological significance of isomiRs in different species. Biocomputational identification of isomiRs using suitable online software/tools (miR-isomiRExp, miRPro, isomiRBank, isomiR-SEA etc) has been followed by empirical validation and pathway analyses. Conclusion: IsomiRs have been associated with various disease-pathways and thus could be used as promising disease-related markers in humans and livestock. In addition, the involvement of isomiRs in cancer and other diseases has been the major topic of interest due to the involvement of different biogenesis pathways.

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“…In general, 3 -isomiRs are more abundant than 5 -isomiRs, however, a number of microRNAs do have prevalent 5 -isomiRs [75][76][77][78]. Since a microRNA's 5 -end determines its seed sequence, 5 -isomiRs have an altered targetome compared to the canonical microRNA sequence and are thus functionally different ( Figure 2) [67,[79][80][81]. While 3 -isomiRs do not have an altered seed sequence, their 3 -end variability has been associated with altered microRNA stability and turnover [82][83][84][85][86].…”

Section: Isomirsmentioning

confidence: 99%

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Kwast

Quax

Nossent

2019

Cells

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Therapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of preexisting collateral arterioles into fully functional arteries. Both angiogenesis and arteriogenesis are highly multifactorial processes that require a multifactorial regulator to be stimulated simultaneously. MicroRNAs can regulate both angiogenesis and arteriogenesis due to their ability to modulate expression of many genes simultaneously. Recent studies have revealed that many microRNAs have variants with altered terminal sequences, known as isomiRs. Additionally, endogenous microRNAs have been identified that carry biochemically modified nucleotides, revealing a dynamic microRNA epitranscriptome. Both types of microRNA alterations were shown to be dynamically regulated in response to ischemia and are able to influence neovascularization by affecting the microRNA’s biogenesis, or even its silencing activity. Therefore, these novel regulatory layers influence microRNA functioning and could provide new opportunities to stimulate neovascularization. In this review we will highlight the formation and function of isomiRs and various forms of microRNA modifications, and discuss recent findings that demonstrate that both isomiRs and microRNA modifications directly affect neovascularization and vascular remodeling.

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Characterizing isomiR variants within the microRNA‐34/449 family

Cited by 48 publications

References 54 publications

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Biogenesis and biological implications of isomiRs in mammals- a review

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

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