MicroRNA-185 regulates chemotherapeutic sensitivity in gastric cancer by targeting apoptosis repressor with caspase recruitment domain

Q, Li; Jx, Wang; Yq, He; Chen, Feng; Xj, Zhang; Jq, Sheng; Pf, Li

doi:10.1038/cddis.2014.148

Cited by 70 publications

(52 citation statements)

References 46 publications

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“…In a gastric cancer study, a novel mechanism whereby miR‐185 directly targets apoptosis repressor with caspase recruitment domain (ARC) was revealed. The role of this miRNA was studied in vitro and further validated in a gastric tumor xenograft model …”

Section: Mirnas Are Involved In All Cancer Hallmarksmentioning

confidence: 99%

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MicroRNAome genome: A treasure for cancer diagnosis and therapy

Berindan‐Neagoe

Monroig

Pasculli

et al. 2014

CA A Cancer J Clinicians

439

381

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The interplay between abnormalities in genes coding for proteins and microRNAs (miRNAs) has been among the most exiting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as these molecules produced from what was once considered “genomic trash”, have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development and differentiation at the transcriptional, post-transcriptional and/or translational level. In this review article we present miRNAs as ubiquitous players involved in all cancer hallmarks. We also describe the most used methods to detect their expression, which have revealed through gene expression studies the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, we discuss the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment-response. Along with this, we explore current strategies in designing miRNA-targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, we introduce a new wave in molecular oncology translational research, the study of long non-coding RNAs.

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Section: Mirnas Are Involved In All Cancer Hallmarksmentioning

confidence: 99%

“…The role of this miRNA was studied in vitro and further validated in a gastric tumor xenograft model. 71…”

Section: Evasion From Apoptosismentioning

confidence: 99%

MicroRNAome genome: A treasure for cancer diagnosis and therapy

Berindan‐Neagoe

Monroig

Pasculli

et al. 2014

CA A Cancer J Clinicians

439

381

View full text Add to dashboard Cite

show abstract

“…MicroRNAs (miRNAs) are a family of small, non-coding RNAs that negatively regulate the expression of target genes by altering mRNA translation or stability [4]. miRNAs play important roles in a wide variety of physiological or pathological processes, including tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-449a Inhibits Proliferation and Induces Apoptosis by Directly Repressing E2F3 in Gastric Cancer

Zhang

et al. 2015

Cell Physiol Biochem

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Background: MicroRNA-449a is a tumor suppressor that is down-regulated in multiple tumors types. However, the role of miR-449a in gastric cancer (GC) remains largely unknown. Methods: MiR-449a expression was up-regulated using miR-449a mimics, and the role of miR-449a in GC was assessed using cell viability and apoptosis assays. miR-449a target genes were confirmed using luciferase activity, RT-PCR and western blot assays. Results: miR-449a was downregulated in gastric cancer cell lines and gastric cancer tissues. Restoration of miR-449a expression inhibited gastric cancer cell proliferation and colony formation. Significant G0/G1 arrest was observed in gastric cancer cells transfected with miR-449a mimics. Furthermore, combination therapy with miR-449a with cisplatin displayed greater anti-tumor effects than treatment with cisplatin alone. We also identified E2F3 (E2F transcription factor 3), an important transcription factor involved in the proliferation and metastasis of tumor cells, as a direct target gene of miR-449a. Furthermore, silencing E2F3 elicits similar a repressive effect as overexpression of miR-449a in gastric cancer cells, and E2F3 overexpression rescued the repressing effects of miR-449a mimics. Conclusions: This study indicates that the miR-449a/E2F3 axis plays an important role in proliferation and apoptosis in gastric cancer. Therefore, miR-449a represents a novel target for gastric cancer therapy.

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“…As the enzymatic product of SPS-2 is part of the selenoprotein biosynthesis machinery, these findings indicate that Se availability affects the selenoproteome in part through epigenetic mechanisms involving miRNA-185 and possibly other miRNAs. miRNA-185 is a particularly interesting target of Se, as it has recently emerged as a tumor suppressor that is frequently downregulated in ovarian, breast, renal, 81 prostate, 82 and gastric cancers, 83 and targets oncogenes, e.g., Six1, 81 androgen receptor, 82 and apoptosis repressor with caspase recruitment domain (ARC). 83 Se has been shown to act anticarcinogenic in experimental settings and also in some human studies ( 18 for an overview); it will therefore be an interesting area of future work to uncover putative roles of miRNAs as mediators of Se-dependent tumor protection against malignant transformation.…”

Section: Regulation Of Microrna Expression By Seleniummentioning

confidence: 99%