OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers

Monroig-Bosque, Paloma del C.; Shah, Maitri; Fu, Xiao; Fuentes‐Mattei, Enrique; Ling, Hui; Ivan, Cristina; Nouraee, Nazila; Huang, Beibei; Chen, Lu; Pileczki, Valentina; Redis, Roxana S.; Jung, Eun Jung; Zhang, Xinna; Lehrer, Michael; Nagvekar, Rahul; Mafra, Ana Carolina Paschoalini; Monroig-Bosque, Maria del Mar; Irimie, Alexandra Iulia; Rivera, Carlos A. Santiago; Dumitru, Calin Dan; Berindan‐Neagoe, Ioana; Nikonowicz, Edward P.; Zhang, Shuxing; Calin, George A.

doi:10.1038/s41598-018-30989-3

Cited by 26 publications

(16 citation statements)

References 41 publications

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“…Exploiting RNA as a drug target has been strongly advocated in antiviral and antibacterial research for >25 yr (for review, see Gallego and Varani 2001;Thomas and Hergenrother 2008;Aboul-ela 2010;Guan and Disney 2012) but not yet reduced to practice. Small molecules or peptidic or antisense molecules targeting ncRNAs may provide an alternative approach to oligonucleotides (Gumireddy et al 2008;Chirayil et al 2009;Zhang et al 2010;Velagapudi and Disney 2014;Shortridge et al 2017;Monroig-Bosque et al 2018), and several lines of evidence suggest that the challenges, while significant, are not insurmountable (Blount and Breaker 2006;Wilson 2014). RNA can be readily selected to recognize small molecules with greater sensitivity to fine details of the chemistry than antibodies (Warner et al 2014).…”

Section: Exploiting Ncrna Structures For Therapeutic Developmentsmentioning

confidence: 99%

Decrypting noncoding RNA interactions, structures, and functional networks

et al. 2019

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The world of noncoding RNAs (ncRNAs) is composed of an enormous and growing number of transcripts, ranging in length from tens of bases to tens of kilobases, involved in all biological processes and altered in expression and/or function in many types of human disorders. The premise of this review is the concept that ncRNAs, like many large proteins, have a multidomain architecture that organizes them spatially and functionally. As ncRNAs are beginning to be imprecisely classified into functional families, we review here how their structural properties might inform their functions with focus on structural architecture-function relationships. We will describe the properties of "interactor elements" (IEs) involved in direct physical interaction with nucleic acids, proteins, or lipids and of "structural elements" (SEs) directing their wiring within the "ncRNA interactor networks" through the emergence of secondary and/or tertiary structures. We suggest that spectrums of "letters" (ncRNA elements) are assembled into "words" (ncRNA domains) that are further organized into "phrases" (complete ncRNA structures) with functional meaning (signaling output) through complex "sentences" (the ncRNA interactor networks). This semiotic analogy can guide the exploitation of ncRNAs as new therapeutic targets through the development of IE-blockers and/or SE-lockers that will change the interactor partners' spectrum of proteins, RNAs, DNAs, or lipids and consequently influence disease phenotypes.

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Section: Exploiting Ncrna Structures For Therapeutic Developmentsmentioning

confidence: 99%

Decrypting noncoding RNA interactions, structures, and functional networks

et al. 2019

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“…In recent studies, xist has been shown to target corresponding miRNAs and regulate the pathological process of various diseases. Xist protects cardiomyocyte hypertrophy by targeting miR-330-3p and modulates myocardial infarction by targeting miR-130a-3p † [15]. However, the mechanism of xist in sepsis -induced myocardial damage remains unclear.…”

Section: Ivyspringmentioning

confidence: 99%

“…Xist plays an essential role in the proliferation, migration, apoptosis, and differentiation of various human cells [26]. Findings from a recent study posit that xist in myocardial cells is up-regulated after myocardial infarction, and knockdown of xist protects against cell death induced by myocardial infarction [15]. Moreover, xist is significantly up-regulated after spinal cord injury [27].…”

Section: Xist Impact Cardiomyocyte Apoptosismentioning

confidence: 99%

Down-regulation of Xist and Mir-7a-5p improves LPS-induced myocardial injury

Liang¹,

Jin²,

Lin³

et al. 2020

Int. J. Med. Sci.

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Background: X-inactive specific transcript (Xist) is a lncRNA, which plays a significant role in X-chromosome inactivation, regulates cell proliferation in tumor cells, and inhibits apoptosis in acute myocardial infarction. On the other hand, miR-7a-5p is involved in cardiomyocytes injury in myocardial ischemia/reperfusion. However, their roles in LPS-induced damage remain unclear. Objectives: This study aimed at using siRNA transfection and lentivirus infection to regulate the expression of xist and miR-7a-5p, and to evaluate their effects on LPS-induced myocardial damage. Method: Mice cardiomyocytes (MCM) cells were divided into six groups, namely the control group, the LPS group, the LPS + lncRNAgroup, the LPS + lncRNA + group, the LPS + miRNAgroup, and the LPS + miRNA + group. Quantitative real-time PCR (qRT-PCR) was performed to assay for the RNA expressions of xist, miR-7a-5p, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and recombinant mitochondrial transcription factor A (Tfam) in all the groups. The ATP level was determined using the adenosine triphosphate (ATP) assay kit according to the manufacturer's instructions. Flow cytometry was performed to estimate the level of apoptosis and proliferation in cells in each group. Results: The level of xist in the myocardial cells was markedly higher in the LPS group compared with the control group; however, it was reduced in the LPS+ lncRNAgroup. There was no significant difference in the expression of xist among the LPS+miRNA-, LPS+miRNA + , and LPS groups. Moreover, the expression of mir-7a-5p was significantly reduced in myocardial cells in the LPS group, and moderately reduced in the LPS+ miRNAgroup, but remarkably elevated in the LPS+ miRNA + group (P<0.05). The expression of mir-7a-5p was comparably similar in the LPS+ lncRNAgroup, LPS+ lncRNA + group, and LPS groups. Further, the levels of PGC-1a, and Tfam were determined. In the LPS group, the expression of PGC-1α was significantly reduced but elevated in the LPS+lncRNA-and LPS+ miRNAgroups (P<0.05). There was no significant difference in the level of PGC-1α among the LPS, LPS+ lncRNA + , and LPS+ miRNA + groups. The expression of Tfam was markedly reduced in the LPS group (P < 0.05), but elevated after the suppression of xist and mir-7a-5p. The expression of Tfam was not significantly different among the LPS group, LPS+ lncRNA + and LPS+ miRNA + groups. Notably, overexpression of mir-7a-5p had a mild effect on the expression of Tfam in the LPS+ miRNA + group compared with the control group. Besides, ATP expression in the LPS group was markedly reduced, but elevated after the inhibition of xist and mir-7a-5p. Suppressing the expression of xist or mir-7a-5p resulted in reduced cell apoptosis and increased cell proliferation. Conclusions: In this study, we established that down-regulation of xist and mir-7a-5p reduces apoptosis in response to LPS.

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“…We have a deep interest in modeling RNA–protein [ 7 ], RNA–RNA [ 8 ], and RNA–small molecule interactions [ 9 ]. Such profundity will significantly help us elucidate novel molecular mechanisms of tumorigenesis and provide insights for therapeutics discovery and development.…”

Section: Long Non-coding Rna “Entrap” Tumor Suppressor Micrornas Tmentioning

confidence: 99%