Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma

Williams, Marissa; Cheng, Yuen Yee; Kirschner, Michaela B.; Sarun, K.; Schelch, Karin; Winata, Patrick; McCaughan, Brian C.; Kao, Steven; Zandwijk, Nico van; Reid, Glen

doi:10.18632/oncotarget.27010

Cited by 14 publications

(10 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This in turn results in the transcriptional suppression of multiple miRNAs by c-Myc, including miR-15a, miR-16, miR-34a and the miR-29 family (65). This relationship was recently demonstrated directly for miR-16 in MPM (21).…”

Section: Pathways Commonly Dysregulated In Mpm Alter Mirna Levelssupporting

confidence: 55%

“…(12)(13)(14) miR-24-3p ↑ ↑ N.D. √ ( √ ) Promotes migration and tumor growth in mice; targets CGN Oncomir (15) miR-29c-5p ↓ N.D. High Exp = LS √ -Mimic inhibits growth and migration; targets DNMT1/3A TS (16) miR-31-5p ↓ ↓ High Exp = SS √ -Mimic inhibits growth and migration; targets PPP6C; role in drug resistance TS? (17)(18)(19) miR-34a-5p ↓ ↓ N.D. √ √ i Lost in genetically modified mouse model; targets c-Met TS (20)(21)(22)(23) miR-34b-3p ↓ ↓ N.D. √ √ Inhibits MPM growth, enhance radiosensitivity; inhibitors promote mesothelial proliferation TS (21,22,(24)(25)(26) suppressor activity in two MPM cell lines in vitro, by inhibition of proliferation and migration/invasion. The same mimic led to downregulation of the DNA methyltransferases DNMT3A and DNMT3B, as well as increasing expression of upstream signaling molecules including adiponectin.…”

Section: Modulating Microrna Levels In Mpm Tumor Suppressor Mirnas-eamentioning

confidence: 99%

See 1 more Smart Citation

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

2020

Self Cite

View full text Add to dashboard Cite

microRNAs (miRNAs) are an important class of non-coding RNA that post-transcriptionally regulate the expression of most protein-coding genes. Their aberrant expression in tumors contributes to each of the hallmarks of cancer. In malignant pleural mesothelioma (MPM), in common with other tumor types, changes in miRNA expression are characterized by a global downregulation, although elevated levels of some miRNAs are also found. While an increasing number of miRNAs exhibit altered expression in MPM, relatively few have been functionally characterized. Of a growing number with tumor suppressor activity in vitro, miR-16, miR-193a, and miR-215 were also shown to have tumor suppressor activity in vivo. In the case of miR-16, the significant inhibitory effects on tumor growth following targeted delivery of miR-16-based mimics in a xenograft model was the basis for a successful phase I clinical trial. More recently overexpressed miRNAs with oncogenic activity have been described. Many of these changes in miRNA expression are related to the characteristic loss of tumor suppressor pathways in MPM tumors. In this review we will highlight the studies providing evidence for therapeutic effects of modulating microRNA levels in MPM, and discuss these results in the context of emerging approaches to miRNA-based therapy.

show abstract

Section: Pathways Commonly Dysregulated In Mpm Alter Mirna Levelssupporting

confidence: 55%

Section: Modulating Microrna Levels In Mpm Tumor Suppressor Mirnas-eamentioning

confidence: 99%

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…S1). It has previously been shown that the DLEU2/miR-15a/miR-16-1 locus contributed to cell apoptosis and progression in liver fibrosis (10), modulated miR-30a sponging in clear cell renal cell carcinoma (11), and miR-15a/16 suppression was implicated in the development of pleural mesothelioma (25).…”

Section: Introductionmentioning

confidence: 99%

Screening for alternative splicing of lncRNA Dleu2 in the mouse liver cell line AML-12

2021

View full text Add to dashboard Cite

The long non coding RNA deleted in leukemia 2 gene (Dleu2) has recently been demonstrated to be an active player in the progression of several types of cancer, including hepatocellular carcinoma. Dleu2 may serve a role in modulating the downstream effects-mediated by alternative splicing of its multiple exons. However, the proportional expression of these alternative splicing populations of the Dleu2 exons is currently unknown. To determine how Dleu2 could be affected by alternative splicing, a series of alternative splicing primer sets were designed to investigate which transcripts were preferentially activated when Dleu2 was targeted for downregulation or upregulation. A specific Dleu2 small interfering RNA that targeted an exon upstream of the tumor suppressor microRNA site significantly knocked down Dleu2 expression across all the primer sets used, which targeted 13 different alternative splicing transcripts over 5 different promoter sites in the mouse liver cell line, AML-12. Similarly, 50 µM Resveratrol led to significant upregulation of Dleu2 in 11 alternative splicing transcripts. These results show that Dleu2 is capable of successful modulation across alternative splicing transcripts that can be screened, and also that Resveratrol can be a potential nutraceutical, which may potentially lead to novel approaches in the use of lncRNA Dleu2 for diagnostics and regulation.

show abstract

“…Studies have proved that miRNAs in the miR-15/16 family have anticancer effect. In malignant pleural mesothelioma, the downregulation of miR-15/16 is due to transcriptional inhibition of c-myc, mainly through the control of mir-15b/16-2 site [8].…”

Section: Introductionmentioning

confidence: 99%

Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2

Jiang

Liu

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Purpose. Aloe-emodin (AE) is a natural compound derived from aloe vera and palmatum rhubarb and shows anticancer activities in various cancers. Bcl-2 family is the main regulator of cell death or cell survival. This study describes the effects of AE on proliferation of breast tumor (BT) cells. Methods. MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 cell lines were exposed to AE. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting. The levels of mRNA and miRNA were examined by RT-PCR. Bioinformatics was applied to screen miRNAs that bind to 3′-UTR of mRNA. Results. The results showed that AE selective activity inhibited the proliferation and induced apoptosis of MCF-10AT and MCF-7 cells but exhibited no significant inhibition in MCF10A and MDA-MB-231 cells. Mechanistically, AE dose-dependently decreased the protein expression of Bcl-2 and Bcl-xl, while it increased Bax protein expression in MCF-10AT and MCF-7 cells. The levels of Bcl-xl and Bax mRNA were altered by AE treatment, which was consistent with the protein expression results. However, Bcl-2 mRNA levels were not affected in either cell line, suggesting that AE may modulate the protein translation of Bcl-2 through miRNAs. In all candidate miRNAs that bind to 3′-UTR of Bcl-2, miR-15a and miR-16-1 were dose-dependently downregulated by AE. Moreover, inhibition of miR-15a/16-1 could eliminate the inhibition of MCF-10AT and MCF-7 cells growth by AE and could reverse the downregulation of AE-induced Bcl-2 protein level. Conclusion. Our research provides an important basis that AE induces BT cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2.

show abstract

Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma

Cited by 14 publications

References 57 publications

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

Screening for alternative splicing of lncRNA Dleu2 in the mouse liver cell line AML-12

Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2

Contact Info

Product

Resources

About