Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Rolfo, Christian; Fanale, Daniele; Hong, David S.; Tsimberidou, Apostolia M.; Piha-Paul, Sarina A.; Pauwels, Patrick; Meerbeeck, Jan P. van; Caruso, Stefano; Bazan, Viviana; Cicero, Giuseppe; Russo, Antonio; Giovannetti, Elisa

doi:10.2174/1389201015666140519123219

Cited by 52 publications

(40 citation statements)

References 106 publications

(116 reference statements)

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“…28 miR-31 and miR-155 significantly inhibited the cisplatin sensitivity in non-small cell lung cancer cells by suppressing ABCB9 and Apaf-1, respectively, 29,30 while miR-451 elevated the cisplatin sensitivity of A549 cells. 31 Moreover, miR-98 sensitized cisplatin-resistant A549/DDP cells via upregulation of HMGA2.…”

Section: Discussionmentioning

confidence: 91%

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

Huang

Chen

et al. 2016

Cell Cycle

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Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down-regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR33b-3p endowed the lung cancer cells with enhanced survival and decreased gH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers.

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Section: Discussionmentioning

confidence: 91%

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

Huang

Chen

et al. 2016

Cell Cycle

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“…However, the recent discovery of microRNA may improve the knowledge about the complex control of gene expression, and help to clarify the role of different signaling pathways, involved in oncogenesis and drug resistance, in different tumor types, including NSCLC [100].…”

Section: Expert Opinionmentioning

confidence: 99%

On the pharmacogenetics of non-small cell lung cancer treatment

Santarpía

Rolfo

Peters

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction. Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/ acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. The present review summarizes the main findings on NSCLC pharmacogenetics, critically reappraising the most important studies on polymorphisms correlated with outcome of pemetrexed and EGFR-inhibitors, and provides perspective on clinical application of genomic tests for treatment decision-making. Expert Opinion. A major challenge in NSCLC is the identification of subgroups of diseases/patients that will truly benefit from specific treatments. Ideally, convenient and minimally invasive tests to decipher biomarkers of chemosensitivity/resistance and toxicity should be developed alongside novel anticancer treatments. Integration with the latest generation of whole-genome analyses and liquid biopsies as well as prospective validation in large cohorts of patients will overcome the limitations of the traditional pharmacogenetic approaches. ARTICLE HISTORY

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“…Accumulating evidence has indicated that microRNAs (miRNAs or miRs) serve a role in a number of cancer processes, including lung cancer (8)(9)(10). The results of previous studies have demonstrated that targeting or regulating miRNAs may identify novel ways to effectively overcome lung cancer resistance and personalize lung cancer therapy (11,12).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-122-3p inhibits tumor cell proliferation and induces apoptosis by targeting Forkhead box O in A549 cells

Wen

Yang

et al. 2017

Oncol Lett

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Abstract. The imbalance between cell proliferation and apoptosis was implicated to serve key roles in cancer pathogenesis. The characteristics of microRNAs (miRNAs/miRs) have attracted much attention in research focusing on cancer pathogenesis in recent years. miR-122-3p has been reported to be associated with a number of disease processes and pathogenesis, including lung cancer. The present study aimed to investigate the association of miR-122-3p expression level with cell proliferation and apoptosis in a lung cancer cell line. A549 cells were transfected with miR-122-3p to interrupt the expression of miR-122-3p. Subsequently, MTT and BrdU assay, and western blot were used to analyze the influence of miR-122-3p on lung cancer cell proliferation, cell viability and its underlying mechanism. The present study revealed that, by targeting p27, overexpression of miR-122-3p inhibited cell proliferation in lung cancer. Furthermore, the cell apoptosis analysis suggested that overexpression of miR-122-3p was able to inhibit cell apoptosis by targeting Forkhead box O. These findings suggest that miR-122-3p may be associated with the pathology and progression of lung cancer and be a new therapeutic target for this disease.

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Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Cited by 52 publications

References 106 publications

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

On the pharmacogenetics of non-small cell lung cancer treatment

MicroRNA-122-3p inhibits tumor cell proliferation and induces apoptosis by targeting Forkhead box O in A549 cells

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Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Cited by 52 publications

References 106 publications

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

On the pharmacogenetics of non-small cell lung cancer treatment

MicroRNA-122-3p inhibits tumor cell proliferation and induces apoptosis by targeting Forkhead box O in A549 cells

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DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21^WAF1/CIP1