International Journal of Molecular Sciences

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Non-small Cell Lung Cancer

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Dear Colleagues,

Lung cancer is the leading cause of cancer-related death worldwide. It is divided into two groups: small-cell lung cancer and non-small lung cancer (NSCLC). NSCLC accounts for approximately 80% of all lung cancer and is further divided into four major histopathologic groups: squamous, adenocarcinoma, adenosquamous and large cell. With the increased screening of high-risk patients, modern diagnostic tools, and the development of new treatment strategies, including targeted therapies and immunotherapies, mortality from lung cancer is declining. However, approximately 40% of NSCL are diagnosed at an advanced stage, and consequently have a poor prognosis and overall survival. To improve overall survival, detection of accurate biomarkers is required. Recently, microRNAs (miRNAs) have been investigated as potential biomarkers for diagnosis, predictors of prognosis and response to therapy for NSCLC. miRNAs are small noncoding RNA about 10–22 nucleotides in length that function as post-transcriptional regulators of gene expression and have important roles in almost all biological pathways, including development, differentiation, cell cycle, proliferation, invasion and metastasis.

This Special Issue on “Non-Small Cell Lung Cancer” will focus on the recent advancement in non-small cell lung cancer and the potential of miRNAs for the development of novel cancer therapy, including miRNA delivery systems.

Dr. Inamul Haque
Guest Editor

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Keywords

MicroRNA
Non-small cell lung cancer
Biomarkers
miRNA-delivery system.

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14 pages, 3305 KiB

Open AccessCommunication

Effects of miRNA-149-5p and Platelet-Activating Factor-Receptor Signaling on the Growth and Targeted Therapy Response on Lung Cancer Cells

by Shreepa J. Chauhan, Anita Thyagarajan and Ravi P. Sahu

Int. J. Mol. Sci. 2022, 23(12), 6772; https://doi.org/10.3390/ijms23126772 - 17 Jun 2022

Cited by 2 | Viewed by 1826

Abstract

Accumulating evidence indicates that microRNAs (miRs) play critical roles in essentially all biological processes and their altered expression has been documented in various disease conditions, including human malignancies. Although several cellular mechanisms have been identified in mediating the effects of miRs, the involvement of G-protein-coupled, platelet-activating factor-receptor (PAFR) signaling in miR-149-5p-induced effects on lung cancer growth and therapeutic potential has not been studied. To that end, we first evaluated the functional significance of PAFR and miR-149-5p in A549 and H1299 human non-small cell lung cancer (NSCLC) cell lines. We observed that these tumor lines express endogenous PAFR and miR-149-5p and that PAFR activation by PAF agonist (CPAF) significantly increased, whereas miR-149-5p mimic transfection inhibited cell proliferation in a dose-dependent manner. Interestingly, miR-149-5p mimic significantly attenuated CPAF-mediated increased proliferation of NSCLC cells, as confirmed by miR-149-5p, cyclin D1, and forkhead box protein M1 (FOXM1) expression analysis via qPCR. Our next studies examined PAFR- and miR-149-5p-mediated effects on targeted therapy (i.e., erlotinib and gefitinib) responses. We observed that erlotinib and gefitinib inhibited A549 and H1299 cell survival in a dose- and time-dependent manner, and CPAF significantly blocked this effect. These findings indicate that miR-149-5p blocks PAFR-mediated increased cell proliferation, and PAFR activation attenuates the cytotoxic effects of targeted therapy. Full article

(This article belongs to the Special Issue Non-small Cell Lung Cancer)

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28 pages, 6048 KiB

Open AccessArticle

Identification of Prognostic and Chemopredictive microRNAs for Non-Small-Cell Lung Cancer by Integrating SEER-Medicare Data

by Qing Ye, Joseph Putila, Rebecca Raese, Chunlin Dong, Yong Qian, Afshin Dowlati and Nancy Lan Guo

Int. J. Mol. Sci. 2021, 22(14), 7658; https://doi.org/10.3390/ijms22147658 - 17 Jul 2021

Cited by 11 | Viewed by 3066

Abstract

This study developed a novel methodology to correlate genome-scale microRNA (miRNA) expression profiles in a lung squamous cell carcinoma (LUSC) cohort (n = 57) with Surveillance, Epidemiology, and End Results (SEER)-Medicare LUSC patients (n = 33,897) as a function of composite tumor progression indicators of T, N, and M cancer stage and tumor grade. The selected prognostic and chemopredictive miRNAs were extensively validated with miRNA expression profiles of non-small-cell lung cancer (NSCLC) patient samples collected from US hospitals (n = 156) and public consortia including NCI-60, The Cancer Genome Atlas (TCGA; n = 1016), and Cancer Cell Line Encyclopedia (CCLE; n = 117). Hsa-miR-142-3p was associated with good prognosis and chemosensitivity in all the studied datasets. Hsa-miRNA-142-3p target genes (NUP205, RAN, CSE1L, SNRPD1, RPS11, SF3B1, COPA, ARCN1, and SNRNP200) had a significant impact on proliferation in 100% of the tested NSCLC cell lines in CRISPR-Cas9 (n = 78) and RNA interference (RNAi) screening (n = 92). Hsa-miR-142-3p-mediated pathways and functional networks in NSCLC short-term survivors were elucidated. Overall, the approach integrating SEER-Medicare data with comprehensive external validation can identify miRNAs with consistent expression patterns in tumor progression, with potential implications for prognosis and prediction of chemoresponse in large NSCLC patient populations. Full article

(This article belongs to the Special Issue Non-small Cell Lung Cancer)

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