Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth

Harel, Shaul; Ben-Moshe, Noa Bossel; Aylon, Yael; Bublik, Debora Rosa; Moskovits, Neta; Toperoff, Gidon; Azaiza, D; Biagoni, F; Fuchs, Gilad; Wilder, Sylvia; Hellman, Asaf; Blandino, Giovanni; Domany, Eytan; Oren, Moshe

doi:10.1038/cdd.2014.221

Cited by 66 publications

(54 citation statements)

References 53 publications

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“…The association of a series of miRNAs with cellular apoptosis has been previously experimentally verified (25)(26)(27). In the present study, it was demonstrated that miR-1915-3p was a candidate regulator of lung cancer cell apoptosis.…”

Section: A B Discussionsupporting

confidence: 64%

MicroRNA-1915-3p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2

Zhang

et al. 2015

Molecular Medicine Reports

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Micro (mi)RNAs are short non‑coding RNA molecules, which post‑transcriptionally regulate gene expression and exert key roles in cell growth, differentiation and apoptosis. In the present study, the mechanism and the function of miR‑1915‑3p in the apoptotic regulation of lung cancer cell lines (NCI‑H441 and NCI‑H1650) were investigated. The expression analysis confirmed that the expression of miR‑1915‑3p was markedly decreased in the apoptotic cells. The overexpression of miR‑1915‑3p in the lung cancer cells prevented apoptosis induced by etoposide. Developmentally regulated GTP‑binding protein 2 (DRG2) and pre‑B cell leukemia homeobox 2 (PBX2) were identified as downstream targets of miR‑1915‑3p, which was shown to bind directly to the 3'‑untranslated region of DRG2 and PBX2, subsequently lowering their mRNA and protein expression levels. Co‑expression of miR‑1915‑3p and DRG2/PBX2 in the NCI‑H441 and NCI‑H1650 cells partly circumvented the effect of miR‑1915‑3p on apoptosis. The results in the present study revealed that miR‑1915‑3p functions as a silencer of apoptosis, which regulates lung cancer apoptosis via targeting DRG2/PBX2, and consequently this miRNA may be a putative therapeutic target in lung cancer.

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Section: A B Discussionsupporting

confidence: 64%

MicroRNA-1915-3p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2

Zhang

et al. 2015

Molecular Medicine Reports

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“…There have also been multiple reports on the role of miR‐486 in tumorigenesis, some concluding that it acts as a tumor suppressor of LUSC . miR‐515 has also been reported as a tumor suppressor, and similarly, studies have shown that miR‐512 not only inhibits glycolysis but also accelerates apoptosis . So far, there are few reports of a role for miR‐516 or miR‐525 in LUSC, however, there is evidence that they can regulate target genes in other tumors to affect protein expression .…”

Section: Discussionmentioning

confidence: 99%

“…[38][39][40] miR-515 has also been reported as a tumor suppressor, 41,42 and similarly, studies have shown that miR-512 not only inhibits glycolysis but also accelerates apoptosis. 43,44 So far, there are few reports of a role for miR-516 or miR-525 in LUSC, however, there is evidence that they can regulate target genes in other tumors to affect protein expression. 45,46 miR-577 affects cell expression by regulating the Wnt signaling pathway, which subsequently affects cell growth and cell viability.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

Gao

Feng

et al. 2019

J of Cellular Biochemistry

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Background With the development in research, the importance of microRNAs (miRNAs) in the occurrence and metastasis, and prognosis of lung squamous cell carcinoma (LUSC) have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics. Materials and methods We downloaded miRNA and messenger RNA samples related to LUSC from The Cancer Genome Atlas (TCGA) database. Following initial data screening and preprocessing, we utilized the R platform and a range of analysis tools (miRDB, TargetScanHuman7.2, DAVID, and Cytoscape_v3.5.1) to analyze the TCGA data and identify highly specific and sensitive biomarkers. Results We finally identified 12 miRNAs and six central genes closely related to the overall survival of patients with LUSC. We found that high expression of 7 miRNAs (miR‐301b, miR‐383, miR‐512, miR‐515, miR‐525, miR‐577, and miR‐5682) and low expression of five miRNAs (miR‐448, miR‐486, miR‐4732,miR‐4732, miR‐516, and miR‐1911) can significantly improve the overall survival rate of patients with LUSC. The six central genes DLGAP5, CENPA, CHEK1, LRRK2, CALB1, and TOP2A are directly or indirectly involved in the formation and metastasis of LUSC and could, therefore, be considered as target genes for drug therapy. Conclusion With the development in research, the importance of miRNAs in the occurrence and metastasis and prognosis of LUSC have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics.

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“…In addition, some studies indicate that micro RNA (miRNA) analysis of exosomes might be useful for the diagnosis of lung adenocarcinoma (69–71) and that particular miRNAs can offer prognostic information in advanced NSCLC. For example, downregulation of miRNA-373 and miRNA-512 has been associated with a poor prognosis (72), miR-208a and miR-1246 with resistance to radiotherapy (73, 74), and miR-221-3p and 222-3p with good response to osimertinib in EGFR mutated patients (75). …”

Section: Exosomesmentioning

confidence: 99%

Liquid Biopsy in Non-Small Cell Lung Cancer

et al. 2016

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Liquid biopsy analyses are already incorporated in the routine clinical practice in many hospitals and oncology departments worldwide, improving the selection of treatments and monitoring of lung cancer patients. Although they have not yet reached its full potential, liquid biopsy-based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information. This review summarizes the techniques available for the isolation and analysis of circulating free DNA and RNA, exosomes, tumor-educated platelets, and circulating tumor cells from the blood of cancer patients, presents the methodological challenges associated with each of these materials, and discusses the clinical applications of liquid biopsy testing in lung cancer.

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Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth

Cited by 66 publications

References 53 publications

MicroRNA-1915-3p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2

MicroRNA-1915-3p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

Liquid Biopsy in Non-Small Cell Lung Cancer

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