MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

Zhao, Yuying; Pang, Weifeng; Yang, Ning; Hao, Ling; Wang, Lei

doi:10.3892/ijo.2018.4576

Cited by 14 publications

(11 citation statements)

References 51 publications

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“…Previous studies have reported that SOX9 is implicated in the regulation of the PI3K/Akt pathway 31,32. Hence, we next attempted to determine whether miR-605 inhibited the activation of the PI3K/Akt pathway in GBM cells by decreasing SOX9 expression.…”

Section: Resultsmentioning

confidence: 97%

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Jia

Wang

Yin

et al. 2019

OTT

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Background Aberrant microRNA (miRNA) expression has been widely reported to play a crucial role in the progression and development of glioblastoma (GBM). miR-605 has been identified as a tumor-suppressing miRNA in several types of human cancers. Nevertheless, the expression profile and detailed roles of miR-605 in GBM remain unclear and need to be further elucidated. Materials and methods RT-qPCR analysis was utilized for the determination of miR-605 expression in GBM tissues and cell lines. In addition, CCK-8 assay, transwell migration and invasion assays, as well as sub-cutaneous xenograft mouse models were utilized to evaluate the effects of miR-605 upregulation in GBM cells. Notably, the potential mechanisms underlying the activity of miR-605 in the malignant phenotypes of GBM were explored. Results We observed that expression of miR-605 was reduced in GBM tissues and cell lines. Decreased miR-605 expression exhibited significant correlation with KPS score. The overall survival rate in GBM patients with low miR-605 expression was lower than that of patients with high miR-605 expression. Increased miR-605 expression suppressed the proliferation, migration, and invasion of U251 and T98 cells. In addition, miR-605 upregulation impaired tumor growth in vivo. Furthermore, SRY-Box 9 (SOX9) was identified as a direct target gene of miR-605 in U251 and T98 cells. SOX9 expression was shown to exhibit an inverse correlation with miR-605 expression in GBM tissues. Moreover, silencing of SOX9 expression mimicked the tumor-suppressing roles of miR-605 in U251 and T98 cells, while SOX9 restoration rescued the suppressive effects of miR-605 overexpression in the same. Notably, miR-605 suppressed the PI3K/Akt pathway in GBM in vitro and in vivo. Conclusion These results demonstrated that miR-605 acts as a tumor suppressor in the development of GBM by directly targeting SOX9 and inhibiting the activation of the PI3K/Akt pathway, suggesting its potential role as a therapeutic target for GBM.

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Section: Resultsmentioning

confidence: 97%

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Jia

Wang

Yin

et al. 2019

OTT

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“…Additionally, PRLR/Jak2/STAT5 is the main signaling pathway for activation in mammary gland, and PRLR-triggered pro-tumorigenic pathways in BC include the PI3K/AKT pathway [172]. As well, numerous studies have shown that IRS4, CDK12, SPC24, Mfng, Transgelin 2, STX3, SOX4, PAK4, TPX2, MEG3 and miR-21, -93, -106b, -130b, -214, -361-5p, -489, -511, -564 as well as lncRNA-HOTAIR and MALAT1 regulate tumorigenesis, proliferation, apoptosis, invasion, migration, paclitaxel resistance or anti-Her2 therapy (trastuzumab) resistance of BC cells through PI3K/AKT pathway [173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191]. And then, PI3K/AKT inhibitors have gained wide attentions, and a large number of clinical trials may have provided tremendous promises in the treatment of BC patients (shown in Tables 2 and 3).…”

Section: Nct02240212mentioning

confidence: 99%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/ AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

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“…MiR-511-5p has been studied for its tumor-suppressive role in preventing colorectal cancer cell progression by targeting GPR116 50 and lung adenoma-carcinoma cells by targeting oncogene TRIB2 51 . Also, a study has proven that miRNA-511-5p prevents malignant behaviors of breast cancer with a direct effect on SOX9 and PI3/AKT regulatory pathway 52 .…”

Section: Discussionmentioning

confidence: 99%

Identification of Potentially Functional Circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as Prognostic Factor of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis

Morovat¹,

Morovat²,

Ashrafi³

et al. 2021

Preprint

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Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA, and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, some related genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with cancer regulation functions. Ten hub genes (TTK،AURKB, KIF20A، KIF23، CEP55، CDC6، DTL، NCAPG، CENPF، PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significant p-values. In the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic factor for HCC.

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MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

Cited by 14 publications

References 51 publications

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Identification of Potentially Functional Circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as Prognostic Factor of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis

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