Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer

Ahn, Young Ho; Ko, Yoon Ho

doi:10.3390/ijms21228782

Cited by 31 publications

(19 citation statements)

References 131 publications

(164 reference statements)

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“…By directly binding to the 3'-untranslated regions of their target genes, miRNAs can promote translation suppression or degrade mRNAs, thereby regulating gene expression (17). Additionally, miRNAs have an effect on the oncogenesis and progression of NSCLC by controlling a wide range of biological behaviours (18)(19)(20). lncRNAs can operate as competitive endogenous RNAs (ceRNAs) by competitively binding to miRNAs and weakening the miRNA-mediated inhibitory effects on mRNA expression, thereby controlling gene expression at the posttranslational level (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

2021

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Long non-coding RNA SLC25A25 antisense RNA 1 (SLC25A25-AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25-AS1 is implicated in the aggressiveness of non-small cell lung cancer (NSCLC) and the possible underlying mechanism. SLC25A25-AS1 expression in NSCLC was determined by reverse transcription-quantitative PCR. The proliferation, apoptosis, migration and invasion of NSCLC cells were tested in vitro through cell counting kit-8 assay, flow cytometry analysis, Transwell migration and invasion assays, followed by in vivo validation using animal experiments. Additionally, the competitive endogenous RNA theory for SLC25A25-AS1, ) and integrin α2 (ITGA2) was identified using subcellular fractionation, bioinformatics analysis, reverse transcription-quantitative PCR, western blotting, a luciferase assay and RNA immunoprecipitation. As compared with normal lung tissues, increased expression of SLC25A25-AS1 was demonstrated in NSCLC tissues using The Cancer Genome Atlas database.. In addition, SLC25A25-AS1 was overexpressed in both NSCLC tissues and cell lines. High SLC25A25-AS1 expression was markedly associated with shorter overall survival time of patients with NSCLC. SLC25A25-AS1 silencing impeded NSCLC cell proliferation and triggered apoptosis, while restricting cell migration and invasion. Tumour growth in vivo was also impaired by SLC25A25-AS1 silencing. Mechanistically, SLC25A25-AS1 was demonstrated to be an miR-195-5p sponge in NSCLC cells. miR-195-5p mimics decreased ITGA2 expression in NSCLC cells by directly targeting ITGA2, and SLC25A25-AS1 interference decreased ITGA2 expression by sequestering miR-195-5p. Furthermore, the antitumour effects of SLC25A25-AS1 silencing on malignant behaviours were counteracted when ITGA2 was restored or when miR-195-5p was silenced. In summary, by controlling the miR-195-5p/ITGA2 axis, SLC25A25-AS1 served tumour-promoting roles in NSCLC cells. Therefore, the SLC25A25-AS1/miR-195-5p/ITGA2 signalling pathway might be an attractive target for future therapeutic options in NSCLC.

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Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

2021

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“…The clinical outcome of NSCLC remains unsatisfactory due to the high metastasis and recurrence rates ( 4 ). It is well-known that miRNAs play important roles in the progression and development of several diseases, including cancers ( 21 – 23 ). For example, miR4766-5p, miR-1915-3p and miR-615-3p are associated with tumor development in gastric cancer ( 24 – 26 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑1301‑3p promotes the progression of non‑small cell lung cancer by targeting Thy‑1 and predicts poor prognosis of patients

Gao

et al. 2021

Oncol Lett

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The role of microRNA (miR)-1301-3p has been investigated in breast cancer and colorectal cancer. Dysregulation of miR-1301-3p expression in non-small cell lung cancer (NSCLC) is speculated to be associated with tumor progression, which was systemically investigated in the present study. Reverse transcription-quantitative PCR analysis was performed to detect miR-1301-3p expression in 124 paired tissue samples and cultured cell lines. The results demonstrated that miR-1301-3p expression was regulated by transfection with miR-1301-3p mimic or inhibitor, and the proliferation, migration and invasion of the transfected cells were assessed via the Cell Counting Kit-8 and Transwell assays. In addition, miR-1301-3p expression was significantly upregulated in NSCLC tissues and cells compared with normal tissues and normal cells, respectively. Notably, upregulated miR-1301-3p expression in NSCLC tissues was significantly associated with the TNM stage, lymph node metastasis and poor prognosis of patients with NSCLC. Furthermore, upregulated miR-1301-3p expression in NSCLC cells promoted cell proliferation, migration and invasion, the effects of which were reversed following miR-1301-3p knockdown. Thy-1 was identified as a direct target of miR-1301-3p, which serves as a tumor promoter in the progression of NSCLC. Taken together, the results of the present study suggest that upregulated miR-1301-3p expression in NSCLC acts as an independent prognostic factor and a tumor promoter by targeting thy-1, thus provides a potential therapeutic target for NSCLC.

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“…Given the connections between inflammation, lung cancer and COVID-19, we surveyed the literature to evaluate possible epigenetic links. The roles of miRNAs in inflammation [ [202] , [203] , [204] , [205] , [206] , [207] , [208] ] and lung cancer [ [251] , [252] , [253] , [254] ] are well established, and recent literature suggests role of miRNAs in COVID-19 infections as well. For example, it has been suggested that immune responses to various viral respiratory infections, including COVID-19, are characterized by ectopic expression of miRNAs [ 255 ].…”

Section: Micrornas As Epigenetic Regulators Connecting Inflammation mentioning

confidence: 99%

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Ahmad

Manzoor

Siddiqui

et al. 2022

Seminars in Cancer Biology

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Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

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Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer

Cited by 31 publications

References 131 publications

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

MicroRNA‑1301‑3p promotes the progression of non‑small cell lung cancer by targeting Thy‑1 and predicts poor prognosis of patients

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

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