The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

Kalhori, Mohammad Reza; Irani, Shiva; Soleimani, Masoud; Arefian, Ehsan; Kouhkan, Fatemeh

doi:10.1002/jcb.28935

Cited by 30 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the observed reversion of the core miRNA expression levels on differentiation, and, therefore, the loss of stemness properties ( Figure 2B), further support that the five core miRNAs identified are regulators of CSC stemness properties. Except for miR-224, the other four miRNAs have previously been reported to be tumor suppressors [65][66][67][68]. Hence, circRNA knockdown of these tumor suppressor miRNAs shown here ( Figure 5B) is consistent with involvement of circ_0066631 and circ_0082096 in the tumorigenesis process.…”

Section: Discussionsupporting

confidence: 84%

Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

Rengganaten

Huang

Tsai

et al. 2020

IJMS

View full text Add to dashboard Cite

Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA–microRNA (miRNA)–mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA–miRNA–mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.

show abstract

Section: Discussionsupporting

confidence: 84%

Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

Rengganaten

Huang

Tsai

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…miR-579 was obviously associated with overall survival and tumor-specific survival of patients with locally advanced rectal cancer [32]. Upregulation of miR-579 could block proliferation, cell cycle, migration and also trigger the apoptosis of glioblastoma multiform cells [24]. Our study demonstrated that miR-579 was downregulated in OS cells, and transfection with miR-579 mimic inhibited the proliferative, invasion, and EMT capabilities of OS cells, which could be reversed by lncRNA NEAT1 overexpression.…”

Section: Discussionmentioning

confidence: 61%

“…Importantly, emerging evidence has pointed out that miRNAs participate in OS, such as miR-18a-5p, miR-671-5p, miR-1301, and miR-212 [19-22]. MiR-579 was reported to be associated with malignancies, such as breast cancer, ovarian cancer, and human glioblastoma [23][24][25]. However, its function in OS deserves further studies.LncRNAs are proved to serve as competing endogenous RNAs (ceRNAs), which sponges certain miRNAs to mediate its target gene, thus changing the post-transcriptional regulation [1].…”

mentioning

confidence: 99%

Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

Wang

Zhou

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Previous studies have suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis in various human carcinomas, including osteosarcoma (OS). However, the expression and specific role of lncRNA NEAT1 in OS remain unknown. The current study aimed at revealing the role of lncRNA NEAT1 and its related mechanism in OS.Methods: Expression profiles of lncRNAs in OS tissues were constructed, and lncRNA NEAT1 expression was verified with RT-qPCR followed by sub-localization. LncRNA-microRNA (miRNA) and miRNA-mRNA interactions were predicted. Validation was performed using dual luciferase reporter gene assay, and gain-and loss-of-function experiments. The effects of lncRNA NEAT1, miR-579 and MMP13 on the proliferation, migration and invasion, epithelial-mesenchymal transition (EMT) of OS cells were detected using colony formation, cell counting kit-8 (CCK-8), Transwell assays and Western blot analysis. Results: LncRNA NEAT1 overexpression was observed in OS tissues and cell lines which located in the cytoplasm. Transfection-induced downregulation of lncRNA NEAT1/MMP13 or overexpression of miR-579 blocked the progression of OS cells. LncRNA NEAT1 promotes MMP13 through sponging miR-579.Conclusion: LncRNA NEAT1 might be beneficial for OS aggravation via sponging miR-579 and facilitating MMP13 expression, which represents a candidate marker and target for OS therapy.clarify the invisible mechanism underlying tumorigenesis and to develop novel molecular targets of OS.Long non-coding RNAs (lncRNAs), surpassing over 200 nucleotides in length, are a prominent class of RNAs exerting a crucial regulatory potential in tumor cell behaviors [6]. Increasing evidence has illustrated that aberrantly expressed lncRNAs were highly associated with the occurrence and development of many human malignancies, including OS [7-9]. Nuclear enriched abundant transcript 1 (NEAT1) is a lncRNA transcribed from the diverse endocrinal neoplasia locus [10]. The interaction of lncRNA NEAT1 has been documented in glioma, prostate cancer and lung adenocarcinoma [11][12][13].LncRNA NEAT1 was also suggested as a tumor promotor in OS by several studies [14][15][16].MicroRNAs (miRNAs) are tiny (~ 22 nucleotides) endogenous non-coding RNA molecules which act at the post-transcriptional level and regulate mRNA expression [17]. They are involved in multiple complicated cellular behaviors [18]. Importantly, emerging evidence has pointed out that miRNAs participate in OS, such as miR-18a-5p, miR-671-5p, miR-1301, and miR-212 [19-22]. MiR-579 was reported to be associated with malignancies, such as breast cancer, ovarian cancer, and human glioblastoma [23][24][25]. However, its function in OS deserves further studies.LncRNAs are proved to serve as competing endogenous RNAs (ceRNAs), which sponges certain miRNAs to mediate its target gene, thus changing the post-transcriptional regulation [1]. However, the concrete influence that lncRNA NEAT1 and miR-579 exerts on OS, especially their interaction is still to be elucidated. In this experimen...

show abstract

“…After 72 h of transduction total RNA was isolated from U251 and A-172 cell lines using the TRIzol reagent (Invitrogen, Carlsbad, CA) according to the company instructions. Complementary DNAs (cDNAs) were manufactured with M-MuLV Reverse Transcription enzyme (Thermo Fisher Scientific, USA) with stem-loop RT primers (for miRNAs and SNORD47) and random hexamers (for genes) 17 . The Real Time-PCR reactions were done using the RealQ Plus 2x Master Mix Green (Ampliqon, Odense M, Denmark) according to the company instructions.…”

Section: Gene Expression Analysismentioning

confidence: 99%

miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines

Kalhori

Arefian

Atanaki

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is the most aggressive and prevalent form of brain tumor cancers that originate from glial cells. This study proposed to investigate the effect of miR-548x and miR-4698 on the proliferation and the PI3K/AKT signaling pathway in glioblastoma cell lines. The molecular features of glioblastoma were studied using KEGG and TCGA sites. Next, by using miRwalk 2.0 and TargetScan version 7.1, the microRNAs that target critical genes in the PI3k/AKT pathway were selected according to score. The pre-miR-548x and pre-miR-4698 were cloned in a pCDH plasmid to produced lentiviral vector. The expression levels of miR-548x, miR-4698 and target genes were detected by qRT-PCR. The MTT, cell cycle, annexin and colony formation assay was used to detect the cell proliferation. MiR-548x and miR-4698 predicted target genes (Rheb, AKT1, mTOR, PDK1) were also evaluated by luciferase assay. The expression of AKT was detected by western blotting. Our results described that overexpression of miR-548x and miR-4698 could inhibit proliferation of A-172 and U251 cells. Also, miR-548x promoted the cell cycle arrest of GBM cell lines. The luciferase reporter assay results showed the 3′ UTR of PDK1, RHEB, and mTOR are direct targets of the miR-548x and miR-4698. Too, the western blot analysis revealed that miR-548x and miR-4698 could downregulate the AKT1 protein expression. Overall, our findings suggest that miR-548x and miR-4698 could function as tumor suppressor genes in glioblastoma by controlling the PI3K/AKT signaling pathway and may act as gene therapy for clinical treatment of glioblastoma multiforme.

show abstract

The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

Cited by 30 publications

References 44 publications

Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

Long noncoding RNA NEAT1 aggravates osteosarcoma carcinogenesis via regulating the microRNA-579/MMP13 axis

miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines

Contact Info

Product

Resources

About