MicroRNA-193b-3p represses neuroblastoma cell growth via downregulation of Cyclin D1, MCL-1 and MYCN

Roth, Sarah Andrea; Hald, Øyvind Holsbø; Fuchs, Steffen; Løkke, Cecilie; Mikkola, Ingvild; Flægstad, Trond; Schulte, Johannes H.; Einvik, Christer

doi:10.18632/oncotarget.24793

Cited by 30 publications

(22 citation statements)

References 71 publications

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“…Transfections were carried out using Lipofectamine 2000 and were performed essentially as described [44]. The following siRNAs were used (all from Qiagen): AllStars Negative Control siRNA (siNC), Hs_MYCN_4 FlexiTube siRNA (siMYCN_1), Hs_MYCN_6 FlexiTube siRNA (siMYCN_2), Hs_TP53_3 FlexiTube siRNA (siTP53_1), and Hs_TP53_9 FlexiTube siRNA (siTP53_2).…”

Section: Methodsmentioning

confidence: 99%

Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma

et al. 2018

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Abnormal increases in nucleolar size and number caused by dysregulation of ribosome biogenesis has emerged as a hallmark in the majority of spontaneous cancers. The observed ribosome hyperactivity can be directly induced by the MYC transcription factors controlling the expression of RNA and protein components of the ribosome. Neuroblastoma, a highly malignant childhood tumor of the sympathetic nervous system, is frequently characterized by MYCN gene amplification and high expression of MYCN and c-MYC signature genes. Here, we show a strong correlation between high-risk disease, MYCN expression, poor survival, and ribosome biogenesis in neuroblastoma patients. Treatment of neuroblastoma cells with quarfloxin or CX-5461, two small molecule inhibitors of RNA polymerase I, suppressed MycN expression, induced DNA damage, and activated p53 followed by cell cycle arrest or apoptosis. CX-5461 repressed the growth of established MYCN -amplified neuroblastoma xenograft tumors in nude mice. These findings suggest that inhibition of ribosome biogenesis represent new therapeutic opportunities for children with high-risk neuroblastomas expressing high levels of Myc.

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Section: Methodsmentioning

confidence: 99%

Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma

et al. 2018

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“…The MYCN gene regulates cell growth, cell proliferation and cell apoptosis. Thus, the MYCN gene is closely related to a variety of cancers, especially NB 8 , 9 . Specifically, MYCN is a genetic biomarker of NB 10 .…”

Section: Introductionmentioning

confidence: 99%

RNA N6-methyladenosine modification is required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression

Cheng

Deng

et al. 2020

Sci Rep

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Neuroblastoma (NB) is one of the most common malignant tumors of the sympathetic nervous system in childhood. NB severely threatens patient’s health and life. However, more effective diagnosis and treatment methods are badly needed in clinics all over the world. MYCN is well recognized as a genetic biomarker of high risk and poor outcome in NB. miRNAs are small RNAs and miR-98 involved in the pathogenesis of various cancers. The role and mechanism of miR-98 in NB remains to be investigated. Here we found that miR-98 was decreased in human MYCN-high-expression NB tissues, and its down-regulation was associated with poor prognosis of NB. Over-expression of miR-98 inhibited cell proliferation, migration and invasion of NB cells. The analysis by employing the software of miRanda predicted the possible binding sites of miR-98 in the 3′-UTR of MYCN , and experimental data illustrated that miR-98 directly bound to MYCN 3′-UTR and decreased MYCN expression. Over-expression of MYCN rescued the decreased malignant phenotype caused by over-expression of miR-98 in NB. N 6 -methyladenosine modification in 3′-UTR of MYCN promoted its interaction with miR-98. The data collectively demonstrated that RNA m 6 A modification was required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression, and miR-98 might be novel targets for NB detection and treatment.

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“…MiR-193b-3p, a mature miRNA derived from the 3ʹ arm of miR-193b precursor (pre-miR-193b), has been widely reported as a tumor suppressor in multiple cancers such as ovarian cancer 30 , neuroblastoma. 31 and acute lymphoblastic leukemia. 32 For instance, the enforced expression of miR-193b-3p suppressed cell proliferation and promoted cell apoptosis by targeting KRAS in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of linc00152 inhibits the progression of gastric cancer by regulating microRNA-193b-3p/ETS1 axis

Wang

Chen

Yang

et al. 2018

Cancer Biology & Therapy

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Background: Gastric cancer (GC) is a serious threat for public health worldwide. Long non-coding RNA (lncRNA) linc00152 has been well reported to be an oncogene and a potential biomarker in multiple cancers including GC. However, the molecular mechanisms of linc00152 in GC development need to be further investigated. Methods: RT-qPCR assay was employed to detect the levels of linc00152, microRNA-193b-3p (miR-193b-3p) and ETS1 mRNA. ETS1 protein level was measured by western blot assay. Cell proliferative, migratory and invasive capacities were assessed by colony formation together with CCK-8 assays, transwell migration and invasion assays, respectively. Bioinformatics analyses and luciferase reporter assay were used to explore whether miR-193b-3p could interact with linc00152 or ETS1 3ʹUTR. The roles and molecular basis of linc00152 silence on the growth of GC xenograft tumors were tested in vivo. Results: Linc00152 expression was notably upregulated in GC tissues and cells. The proliferative, migratory and invasive abilities of GC cells were weakened by linc00152 depletion, miR-193b-3p overexpression or ETS1 knockdown. Linc00152 upregulation inhibited miR-193b-3p expression by direct interaction and abolished miR-193b-3p-mediated anti-proliferation, anti-migration and anti-invasion effects in GC cells. ETS1 was a target of miR-193b-3p and linc00152 could promote ETS1 expression by downregulating miR-193b-3p. In vivo experiments further validated that linc00152 knockdown inhibited the growth of GC xenograft tumors by upregulating miR-193b-3p and downregulating ETS1. Conclusion: Knockdown of linc00152 inhibited GC progression by sequestering miR-193b-3p from ETS1 in vitro and in vivo, elucidating a novel molecular mechanism of linc00152 in promoting GC carcinogenesis.

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MicroRNA-193b-3p represses neuroblastoma cell growth via downregulation of Cyclin D1, MCL-1 and MYCN

Cited by 30 publications

References 71 publications

Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma

Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma

RNA N6-methyladenosine modification is required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression

Knockdown of linc00152 inhibits the progression of gastric cancer by regulating microRNA-193b-3p/ETS1 axis

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