RNAi and RNAa - The Yin and Yang of RNAome

Pushparaj, Peter Natesan; Aarthi, J.J.; Kumar, Srinivasan Dinesh; Manikandan, Jayapal

doi:10.6026/97320630002235

Cited by 33 publications

(24 citation statements)

References 12 publications

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“…Thus, most of the previous functional studies are limited to the knockdown approach [22] . RNA activation-induced gene expression by targeting promoter sequence allowed us to physiologically and directly test the function of a given gene [23–26] . In fact, lentiviral-based delivery of dsRNAs has been reported to activate VEGF expression by targeting promoter sequences in an ischemic mouse model [27] .…”

Section: Discussionmentioning

confidence: 99%

MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9

Yang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

163

140

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Our previous studies have shown that the 3' end of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in colorectal cancer (CRC) cell proliferation and migration/invasion in vitro. The role and mechanism of MALAT1 in CRC metastasis in vivo, however, remain largely unknown. In the present study, we found that MALAT1 was up-regulated in human primary CRC tissues with lymph node metastasis. Overexpression of MALAT1 via RNA activation promoted CRC cell proliferation, invasion and migration in vitro, and stimulated tumor growth and metastasis in mice in vivo. Conversely, knockdown of MALAT1 inhibited CRC tumor growth and metastasis. MALAT1 regulated at least 243 genes in CRC cells in a genome-wide expression profiling. Among these genes, PRKA kinase anchor protein 9 (AKAP-9) was significantly up-regulated at both mRNA and protein levels. AKAP-9 was highly expressed in CRC cells with metastatic potential and human primary CRC tissues with lymph node metastasis, but not in normal cells or tissues. Importantly, knockdown of AKAP-9 blocked MALAT1-mediated CRC cell proliferation, migration and invasion. These data indicate that MALAT1 may promote CRC tumor development via its target protein AKAP-9.

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Section: Discussionmentioning

confidence: 99%

MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9

Yang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

163

140

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“…These include microRNAs (miRNAs), which inhibit protein translation by base-pairing with imperfect complementarity to target sequences within mRNA molecules; PIWIinteracting RNAs (piRNAs), which are involved in gene silencing by targeting transposons in animal germ cells; and small interfering RNAs (siRNAs) or RNA interference (RNAi), which target homologous mRNA sequences to degrade transcripts, leading to post-transcriptional gene silencing [ 3 -5 ]. A new addition can be made to this category, in the form of activating RNAs, the discovery of which was made serendipitously [ 6 ]. While attempting to silence E-cadherin gene transcription, using small double-stranded RNAs (dsRNAs) in human cells, Li et al [ 7 ] observed that several promoter-targeted dsRNA molecules were able to activate gene and protein expression.…”

Section: Introductionmentioning

confidence: 99%

RNA Activation

Zhao

Voutila²,

Habib

et al. 2015

Innovative Medicine

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The ability to manipulate gene expression is invaluable for understanding the molecular pathogenesis of disease as well as for developing novel therapeutics. RNA interference provides a robust platform for the knockdown of a specifi c gene at the post-transcriptional level, but activation of specifi c genes traditionally has been limited to ligand-mediated activation of signal transduction pathways or introduction of exogenous transgenes from expression vectors. Recent work has shown that small RNA molecules targeted to the promoter region of a gene can activate gene expression. This phenomenon, called RNA activation, provides a tool for specifi c activation of endogenous genes, and introduces a new role for noncoding RNAs in the regulation of gene expression. These small RNAs are typically 21-nucleotide duplexes, and have been shown to activate a wide variety of genes in many cell types and across species. The application of this technology will prove invaluable for basic research through gain-of-function studies and potentially targeted gene activation for disease intervention. This chapter will cover what is currently defi ned on the mechanism of RNA activation, and will explore the possible application of this technology for novel therapeutics.

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“…This information also indicates a new obstacle for RNAi, in which siRNAs may undesirably stimulate the expression of off-target genes. Hence, it can be stated that both RNAa and RNAi constitutes the Yin and Yang of the RNAome in living organisms (Pushparaj et al, 2008a). RNAi AS NOVEL THERAPEUTICS -IS IT IMMINENT?…”

Section: Major Challenges Of Rnai Therapeuticsmentioning

confidence: 99%

siRNA, miRNA, and shRNA: in vivo Applications

et al. 2008

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RNA interference (RNAi), an accurate and potent gene-silencing method, was first experimentally documented in 1998 in Caenorhabditis elegans by Fire et al., who subsequently were awarded the 2006 Nobel Prize in Physiology/Medicine. Subsequent RNAi studies have demonstrated the clinical potential of synthetic small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) in dental diseases, eye diseases, cancer, metabolic diseases, neurodegenerative disorders, and other illnesses. siRNAs are generally from 21 to 25 base-pairs (bp) in length and have sequence-homology-driven gene-knockdown capability. RNAi offers researchers an effortless tool for investigating biological systems by selectively silencing genes. Key technical aspects--such as optimization of selectivity, stability, in vivo delivery, efficacy, and safety--need to be investigated before RNAi can become a successful therapeutic strategy. Nevertheless, this area shows a huge potential for the pharmaceutical industry around the globe. Interestingly, recent studies have shown that the small RNA molecules, either indigenously produced as microRNAs (miRNAs) or exogenously administered synthetic dsRNAs, could effectively activate a particular gene in a sequence-specific manner instead of silencing it. This novel, but still uncharacterized, phenomenon has been termed 'RNA activation' (RNAa). In this review, we analyze these research findings and discussed the in vivo applications of siRNAs, miRNAs, and shRNAs.

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RNAi and RNAa - The Yin and Yang of RNAome

Cited by 33 publications

References 12 publications

MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9

MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9

RNA Activation

siRNA, miRNA, and shRNA: in vivo Applications

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