Targeting the SMO oncogene by miR-326 inhibits glioma biological behaviors and stemness

Du, Wei; Liu, Xing; Chen, Lingchao; Dou, Zhijin; Lei, Xuhui; Chang, Liang; Cai, Jinquan; Cui, Yuqiong; Yang, Dan; Sun, Ying; Li, Yongli; Jiang, Chuanlu

doi:10.1093/neuonc/nou217

Cited by 71 publications

(63 citation statements)

References 50 publications

(22 reference statements)

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“…Several miR-326 targets, including Bcl-2 (38) in osteosarcoma, FSCN1 (39) and NOB1 (41) in gastric cancer, SMO (47) and PKM2 (43) in glioma and CCND1 (25), phox2a (44), SP1 (45) and ADAM17 (46) in lung cancer, have been identified. In the present study, KRAS was validated as a novel target of miR-326.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Kang

Zhang

et al. 2017

Oncol Rep

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Abstract. Melanoma is the seventh most common malignancy in females and the fifth most common cancer in males worldwide. An increasing number of studies have reported that microRNA (miRNA) dysregulation is frequently observed in various types of human cancers, including melanoma. Abnormally expressed miRNAs play an important role in melanoma formation and progression by serving as potential biomarkers and therapeutic targets. Recently, miRNA-326 (miR-326) has been reported to be differentially expressed in various types of tissues and play important roles in tumourigenesis and tumour development. However, the expression levels, biological roles and underlying mechanisms of miR-326 in melanoma remain unknown. In the present study, we demonstrated that miR-326 was significantly downregulated in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-326 suppressed melanoma cell proliferation and invasion and increased cell apoptosis in vitro. Using bioinformatic analysis, Kirsten rat sarcoma viral oncogene homolog (KRAS) was predicted as a potential target of miR-326. Luciferase reporter assay confirmed that miR-326 could directly target the 3'-untranslated region of KRAS. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that miR-326 upregulation decreased the KRAS expression in melanoma cells at both the mRNA and protein level. Furthermore, KRAS was upregulated in melanoma tissues and inversely correlated with miR-326 expression. In addition, the KRAS knockdown phenocopied the tumour-suppressing effects of miR-326 overexpression on melanoma cells. The restoration of the expression of KRAS markedly reversed the antitumour effects induced by miR-326 overexpression in melanoma cells. Further experiments indicated that miR-326 inactivated the AKT and ERK signalling pathways in melanoma. Collectively, these results revealed that miR-326 serves as a tumour suppressor in melanoma by targeting KRAS and regulating the AKT and ERK signalling pathways, indicating that miR-326 may be a promising therapeutic target for melanoma patients.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

Kang

Zhang

et al. 2017

Oncol Rep

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“…Было показано, что экспрессия SMO обратно коррелирует с экспрессией miR-326, являясь её прямой мишенью. Более того, гиперэкспрессия miR-326 снижала пролиферативную активность и стволовые свойства культуры ОСК глиомы U251 [20]. При этом miR-326 способна ингибировать сигнальный путь PI3К (phosphatidylinositol 3-kinase) в клетках глиобластомы [21].…”

Section: Smo Gli1 Ptchunclassified

“…Введение miR-326 может являться новой стратегией терапии [35]. miR-326 ингибируется PI3-киназным каскадом [21] [ [20][21][22], [35], [37] miR-675-5p, ген которой находится внутри гена длинной некодирующей РНК Н19, играет роль в развитии ответа на гипоксию и гипоксия-опосредованном ангиогенезе [81] [81], [82] короткая длина зрелых микро-РНК ограничивает дизайн проб [101]. Несомненным преимуществом RNA-seq является возможность глубокого анализа дифференциальной экспрессии, в том числе поиска вариаций (SNP и др.…”

Section: (рис 2)unclassified

The role of micro-RNA in the regulation of signal pathways in gliomas

et al. 2017

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Рисунок 1. Два механизма, используемые микро-РНК для регуляции трансляции. Некоторые miRNA способны полностью комплементарно связываться с таргетными мРНК, что вызывает их деградацию. Микро-РНК также могут быть не полностью комплементарны мишеням, тем самым, трансляция блокируется. Адаптировано из [147].

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“…For this reason, miRNAs or corresponding synthetic RNA sequences are being explored as potential drugs against a variety of human disorders [124]. A qRT-PCR and western blot study at Harbin Medical University demonstrated that Smo was highly expressed in multiple glioma cell lines and this over-expression correlated with poor survival [125]. A previous study demonstrated that miR-326 serves as a negative regulator of the Hh pathway by targeting Gli2 and Smo [126].…”

Section: Biologics As Hedgehog Pathway Inhibitorsmentioning

confidence: 99%

Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics

Maschinot¹,

Pace²,

Hadden³

2015

CMC

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The hedgehog (Hh) pathway is a developmental signaling pathway that is essential to the proper embryonic development of many vertebrate systems. Dysregulation of Hh signaling has been implicated as a causative factor in the development and progression of several forms of human cancer. As such, the development of small molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics has been a major area of research interest in both academics and industry over the past ten years. Through these efforts, synthetic small molecules that target multiple components of the Hh pathway have been identified and advanced to preclinical or clinical development. The goal of this review is to provide an update on the current status of several synthetic small molecule Hh pathway inhibitors and explore the potential of several recently disclosed inhibitory scaffolds.

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Targeting the SMO oncogene by miR-326 inhibits glioma biological behaviors and stemness

Abstract: This work suggests a possible molecular mechanism of the miR- 326/SMO axis, which can be a potential alternative therapeutic pathway for gliomas.

Cited by 71 publications

References 50 publications

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

MicroRNA-326 inhibits melanoma progression by targeting KRAS and suppressing the AKT and ERK signalling pathways

The role of micro-RNA in the regulation of signal pathways in gliomas

Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics

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