C/EBPβ mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas

Pascale, Federica Di; Nama, Srikanath; Muhuri, Manish; Quah, Shan; Ismail, Hisyam M; Chan, Xin Hui Derryn; Sundaram, Gopinath M; Rajkumar, R.; Burke, Brian; Sampath, Prabha

doi:10.1093/nar/gkx1105

Cited by 16 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address the molecular mechanisms underlying miR-138-mediated cell proliferation, CREB1, AKT and mTOR expression was further explored and it was observed that miR-138 can directly bind the 3′-UTR of CREB1 and inhibit the phosphorylation of AKT and mTOR without affecting the total expression levels of AKT and mTOR, forming a miR-138/CREB1/AKT/mTOR interactive network that plays an important role in promoting proliferation and suppressing apoptosis of GBM cells. The aforementioned results are also consistent with those of a previous study demonstrating that the C/EBPβ responsive element is essential for miR-138 to participate in the development of gliomas ( 36 ). The present study strongly suggests that the significant suppression of glioma cell proliferation induced by miR-138 treatment may be attributed to an enhancement of AKT/mTOR-induced apoptosis.…”

Section: Discussionsupporting

confidence: 92%

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

et al. 2020

View full text Add to dashboard Cite

Alterations in the expression of microRNA (miR)-138 have been demonstrated to result in the development of several malignant tumours. However, the possible function of miR-138 in human glioma cells remains unclear. The present study demonstrated that miR-138 was significantly downregulated in 48 human glioma specimens by quantitative PCR analysis. The upregulation of miR-138 exerted significant antiproliferative and anti-invasive effects on glioma cells and promoted their apoptosis. In addition, cAMP response element-binding protein 1 (CREB1) was confirmed as a direct target gene of miR-138 by luciferase gene reporter assay, and the antitumour effect of miR-138 on glioma cells was significantly reversed by CREB1 overexpression. Moreover, the molecular mechanisms underlying the tumour-suppressive role of miR-138 in malignant glioma may be associated with the dephosphorylation of AKT/mTOR caused by the miR-138 upregulation-induced decrease in CREB1 expression in glioma cells. The results of the present study indicated that miR-138 may affect CREB1/AKT/mTOR signalling to regulate the proliferation, apoptosis and invasion of glioma cells and the malignant progression of glioma, thereby suggesting that miR-138 may be a potential target for the treatment of gliomas.

show abstract

Section: Discussionsupporting

confidence: 92%

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, certain studies have reported conflicting data. For example, in glioma, miR-138-5p is overexpressed compared with normal cells, and promotes tumor occurrence, development, metastasis and infiltration while suppressing apoptosis (22)(23)(24). Therefore, miR-138-5p may be a 'dual function' miRNA.…”

Section: Discussionmentioning

confidence: 99%

miR‑138‑5p modulates the expression of excision repair cross‑complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin

et al. 2018

View full text Add to dashboard Cite

The microRNA (miR)-138-5p affects the chemotherapeutic sensitivity of several human cancer types. In the present study, the expression and regulatory mechanisms of miR-138-5p were investigated in the gastric cancer cell line SGC7901 and its cisplatin-resistant derivative SGC7901/DDP. Gene microarray and reverse transcription-quantitative polymerase chain reaction analyses revealed that miR-138-5p was expressed at significantly lower levels in SGC7901/DDP compared with SGC7901 cells. Using computational predictive algorithms, two proteins involved in the nuclear excision repair pathway were identified, excision repair cross-complementing (ERCC)1 and ERCC4, as putative miR-138-5p target genes. Western blot analysis confirmed that ERCC1 and ERCC4 expression levels were inversely proportional to miR-138-5p levels in SGC7901 and SGC7901/DDP cells. Furthermore, ERCC1 and ERCC4 were upregulated in SGC7901 cells expressing miR-138-5p-targeting short hairpin RNA and, conversely, downregulated in SGC7901/DDP cells overexpressing miR-138-5p, confirming that this miRNA regulates ERCC protein levels. Notably, miR-138-5p silencing enhanced the cisplatin resistance of SGC7901 cells, while miR-138-5p overexpression partially reversed the cisplatin resistance of SGC7901/DDP cells. Taken together, these data suggest that miR-138-5p regulates the sensitivity of gastric cancer cells to cisplatin, possibly by modulating expression of the DNA repair proteins ERCC1 and ERCC4.

show abstract

“…Adapted from Pascale et al . 32 . Following stringent washing with 5×, 1x and 0.3x SSC buffers, sections were blocked with 10% Goat serum and further incubated with anti-DIG alkaline phosphatase (Roche) overnight at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression

Nama

Muhuri

Pascale

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

Breast cancer manifests as a spectrum of subtypes with distinct molecular signatures, and different responses to treatment. Of these subtypes, triple-negative breast cancer (TNBC) has the worst prognoses and limited therapeutic options. Here we report aberrant expression of microRNA-138 (miR-138) in TNBC. Increased miR-138 expression is highly specific to this subtype, correlates with poor prognosis in patients, and is functionally relevant to cancer progression. Our findings establish miR-138 as a specific diagnostic and prognostic biomarker for TNBC. OncomiR-138 is pro-survival; sequence-specific miR-138 inhibition blocks proliferation, promotes apoptosis and inhibits tumour growth in-vivo . miR-138 directly targets a suite of pro-apoptotic and tumour suppressive genes, including tumour suppressor candidate 2 (TUSC2). miR-138 silences TUSC2 by binding to a unique 5′-UTR target-site, which overlaps with the translation start-site of the transcript. Over-expression of TUSC2 mimics the phenotype of miR-138 knockdown and functional rescue experiments confirm that TUSC2 is a direct downstream target of miR-138. Our report of miR-138 as an oncogenic driver in TNBC, positions it as a viable target for oligonucleotide therapeutics and we envision the potential value of using antimiR-138 as an adjuvant therapy to alleviate this therapeutically intractable cancer.

show abstract

C/EBPβ mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas

Cited by 16 publications

References 26 publications

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

MicroRNA‑138 modulates glioma cell growth, apoptosis and invasion through the suppression of the AKT/mTOR signalling pathway by targeting CREB1

miR‑138‑5p modulates the expression of excision repair cross‑complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin

MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression

Contact Info

Product

Resources

About