miR-21 inhibition of LATS1 promotes proliferation and metastasis of renal cancer cells and tumor stem cell phenotype

An, Feng; Liu, Yidong; Hu, Yan

doi:10.3892/ol.2017.6746

Cited by 15 publications

(10 citation statements)

References 28 publications

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“…miR-21 is involved in epigenetic regulation of YAP1 at two levels: i) miR-21 suppression results in elevated levels of LATS1/2, which down-regulates YAP through phosphorylation [ 13 ]; ii) computational target prediction identifies homology between miR-21 and 3'-UTR of human YAP1 mRNA ( www.targetscan.org ). RT-qPCR revealed that miR-21 expression was significantly more than 3-fold increased in the muscles from DMD patients (p < 0.0001 vs control muscles).…”

Section: Resultsmentioning

confidence: 99%

“…To validate downstream YAP pathway, Survivin (Birc5) which is one of the prominent target genes of YAP [ 3 , 12 ], and miR-21 which is involved in epigenetic regulation of YAP [ 13 ] were studied. RT-qPCR for Survivin Assay ID Hs01125524_m1 was performed using a standard TaqMan PCR kit procedure on an AB-7300 RT-PCR system (Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

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Hippo signaling pathway is altered in Duchenne muscular dystrophy

et al. 2018

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Hippo signaling pathway is considered a key regulator of tissue homeostasis, cell proliferation, apoptosis and it is involved in cancer development. In skeletal muscle, YAP, a downstream target of the Hippo pathway, is an important player in myoblast proliferation, atrophy/hypertrophy regulation, and in mechano-trasduction, transferring mechanical signals into transcriptional responses. We studied components of Hippo pathway in muscle specimens from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, limb-girdle muscular dystrophy type 2A and type 2B and healthy subjects. Only DMD muscles had decreased YAP1 protein expression, increased LATS1/2 kinase activity, low Survivin mRNA expression and high miR-21 expression. In light of our novel results, a schematic model is postulated: low levels of YOD1 caused by increased inhibition by miR-21 lead to an increase of LATS1/2 activity which in turn augments phosphorylation of YAP. Reduced amount of active YAP, which is also a target of increased miR-21, causes decreased nuclear expression of YAP-mediated target genes. Since it is known that YAP has beneficial roles in promoting tissue repair and regeneration after injury so that its activation may be therapeutically useful, our results suggest that some components of Hippo pathway could become novel therapeutic targets for DMD treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Hippo signaling pathway is altered in Duchenne muscular dystrophy

et al. 2018

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“…(38)(39)(40)(41). As a result, inhibition of the aberrant hyperactivity of miR-21 in tumor tissue leads to global changes in cellular signaling pathways and promotes manifold reinforcement of tumor suppressor protein synthesis, such as PTEN, PDCD4, RhoB, LATS1, MGMT, and TP53, exerting potent antitumor action on several carcinogenesis processes simultaneously (42,43).…”

Section: Discussionmentioning

confidence: 99%

Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

Patutina

Gaponova

Sen’kova

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21–targeted µ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21–regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of µ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of µ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology.

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“…In a study investigating the role of gene copy number variation in relation to the clinical parameters of metastatic CCRCC, the loss of PLG was associated with advanced tumor stage and Fuhrman grade (27). As for the hub miRNAs, miR-21 has been widely studied in renal cancer for its regulatory roles in cellular proliferation and metastasis (28–30). In addition, the hub miRNA, miR-155, was determined to regulate the growth and invasion of CCRCC cells by interacting with E2F transcription factor 2 (31).…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of circular RNA molecular regulatory networks in clear cell renal cell carcinoma

Qin

Zhang

et al. 2019

Mol Med Report

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Increasing evidence has indicated that circular (circ)RNAs participate in carcinogenesis; however, the specific regulatory mechanisms underlying the effects of circRNAs, microRNAs (miRNAs/miRs) and genes on the development of clear cell renal cell carcinoma (CCRCC) remain unclear. In the present study, RNA microarray data from CCRCC tissues and control samples were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas, in order to identify significantly dysregulated circRNAs, miRNAs and genes. The Cancer-Specific circRNA Database was used to explore the interactions between miRNAs and circRNAs, whereas TargetScan and miRDB were employed to predict the mRNA targets of miRNAs. Functional enrichment and prognostic analyses were conducted in R. The results revealed that 324 circRNAs were downregulated, whereas 218 circRNAs were upregulated in cancer. In addition, a circRNA-miRNA-mRNA interaction network was constructed. Gene Ontology analysis of the upregulated genes revealed that these genes were enriched in biological processes, including ‘flavonoid metabolic process’, ‘cellular glucuronidation’ and ‘T cell activation’. The downregulated genes were mainly enriched in biological processes, such as ‘nephron development’, ‘kidney development’ and ‘renal system development’. The hub genes, including membrane palmitoylated protein 7, aldehyde dehydrogenase 6 family member A1, transcription factor AP-2α, collagen type IV α 4 chain, nuclear receptor subfamily 3 group C member 2, plasminogen, Holliday junction recognition protein, claudin 10, kinesin family member 18B and thyroid hormone receptor β, and the hub miRNAs, including miR-21-3p, miR-155-3p, miR-144-3p, miR-142-5p, miR-875-3p, miR-885-3p, miR-3941, miR-224-3p, miR-584-3p and miR-138-1-3p, were significantly associated with CCRCC survival. In conclusion, these results suggested that the significantly dysregulated circRNAs, miRNAs and genes identified in this study may be considered potential biomarkers of the carcinogenesis of CCRCC and the survival of patients with this disease.

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miR-21 inhibition of LATS1 promotes proliferation and metastasis of renal cancer cells and tumor stem cell phenotype

Cited by 15 publications

References 28 publications

Hippo signaling pathway is altered in Duchenne muscular dystrophy

Hippo signaling pathway is altered in Duchenne muscular dystrophy

Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

Construction and analysis of circular RNA molecular regulatory networks in clear cell renal cell carcinoma

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