MiR-18a-downregulated RORA inhibits the proliferation and tumorigenesis of glioma using the TNF-α-mediated NF-κB signaling pathway

Jiang, Yang; Zhou, Jinpeng; Zhao, Junshuang; Hou, Dianqi; Zhang, Haiying; Long, Li; Zou, Dan; Hu, Jiangfeng; Zhang, Ye

doi:10.1016/j.ebiom.2020.102651

Cited by 55 publications

(80 citation statements)

References 48 publications

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“…The hBMECs were maintained in endothelial cell medium (ECM; ScienCell Research Laboratories). Six patient-derived primary glioma stem cells from WHO grade II to IV (grade II: GSC205 and GSC207; grade III: GSC306 and GSC307; grade IV: GSC406 and GSC408) were isolated, and neurosphere cultures were obtained as previously described [23]. The detailed clinicopathological information is presented in Table S2.…”

Section: Cell Culture and Gscs Isolationmentioning

confidence: 99%

“…The sequences of all siRNAs are listed in Table S3. The lentivirus transfection and efficacy measurements were performed as previously described [23].…”

Section: Lentiviral Vector Construction and Transfectionmentioning

confidence: 99%

“…Real-time PCR was performed as previously described [23]. The Mini-BEST Universal RNA Extraction kit (TaKaRa, Kyoto, Japan) was used to extract the total RNA of GSCs.…”

Section: Qrt-pcr (Real-time Quantitative Reverse Transcription Pcr)mentioning

confidence: 99%

“…Western blotting was performed as previously described [23]. Briefly, the total proteins of GSCs or tissues were isolated using a total cell protein extraction kit (KeyGen Biotechnology, Nanjing, China).…”

Section: Western Blottingmentioning

confidence: 99%

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The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

Jiang

Zhou

Zhao

et al. 2020

J Exp Clin Cancer Res

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Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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Section: Cell Culture and Gscs Isolationmentioning

confidence: 99%

“…The sequences of all siRNAs are listed in Table S3. The lentivirus transfection and efficacy measurements were performed as previously described [23].…”

Section: Lentiviral Vector Construction and Transfectionmentioning

confidence: 99%

“…Real-time PCR was performed as previously described [23]. The Mini-BEST Universal RNA Extraction kit (TaKaRa, Kyoto, Japan) was used to extract the total RNA of GSCs.…”

Section: Qrt-pcr (Real-time Quantitative Reverse Transcription Pcr)mentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

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The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

Jiang

Zhou

Zhao

et al. 2020

J Exp Clin Cancer Res

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“…16 miR-18a has a promoting effect on glioma via inhibiting retinoic acid receptor-related orphan receptor A (RORA) and activating the TNF-α mediated NF-κB signaling pathway. 17 Recent studies showed that the biological activity of TSN was related to miRNAs. TSN was reported to inhibit the human oncogenic phenotype of gastric cancer via miR-200a/β-catenin axis.…”

Section: Introductionmentioning

confidence: 99%

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

Wang

Hou

et al. 2020

CMAR

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Background: Glioma is one the most common and aggressive primary tumors of adult central nervous system worldwide, which tends to develop dysplasia and metastasis. Recently, toosendanin (TSN) has shown pharmacological effects in several cancers. However, little is known about the underlying mechanism of the effect of TSN on glioma and its relationship between miRNA in glioma. Methods: Cell proliferation, cell cycle, cell apoptosis and cell migration were analyzed by CCK-8 cell viability, flow cytometry, wound scratch healing, transwell and Western blotting assays, respectively, in vitro. The regulation relationships between TSN and miR-608 or between miR-608 and Notch1 (Notch2) were examined using qRT-PCR, dual-luciferase and Western blotting assays. The functional effects of TSN through regulating miR-608 and Notch1 (Notch2) were further examined using a xenograft tumor mouse model in vivo. Results: After TSN concentration was increased from 50 nM, 100 nM to 150 nM, cell proliferation and cell cycle were gradually reduced, and the cell apoptosis rate was increased in U-138MG or U-251MG cells. Wound-healing and transwell assays results showed that cell migration was significantly inhibited in TSN treatment cells (TSN treatment, 50 nM) compared to control cells. Mechanistic studies revealed that TSN up-regulated the expression of microRNA-608 (miR-608), while down-regulated the expression of miR-608's target, Notch1 and Notch2. Over-expression of Notch1 and Notch2 partly attenuated TSN-induced tumor suppressive function. Moreover, in vivo experiments revealed that TSN treatment led to a significant inhibition of tumor growth, suggesting that it might be a promising drug for the treatment of glioma. Conclusion: In the present study, a novel established functional manner of TSN/miR-608/ Notch1 (Notch2) axis was systematically indicated, which might provide prospective intervention ways for glioma therapy.

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Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment

Franz,

Jötten,

Wührl

et al. 2023

Cancer Reports

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BackgroundColorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases.AimsStudying the expression and cellular function of miR‐18a in metastatic colorectal cancer and association to progression‐free survival.Methods and ResultsColorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT‐PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR‐18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR‐18a was increased 4.38‐fold in liver metastases and 3.86‐fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR‐18a expression in liver metastases had a progression‐free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR‐18a knockdown and cell viability was significantly increased after miR‐18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR‐18a expression receiving 5‐FU, folinic acid or oxaliplatin.ConclusionsHigh expression of miR‐18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.

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MiR-18a-downregulated RORA inhibits the proliferation and tumorigenesis of glioma using the TNF-α-mediated NF-κB signaling pathway

Cited by 55 publications

References 48 publications

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment

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