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MicroRNAs as Biomarkers for Lung Cancer
Summary of Key Points
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The biologic roles of microRNAs (miRNAs) in lung cancer indicate their correlation with disease status, prognosis, and therapeutic outcome. The discovery of miRNAs has opened a new avenue for individualized disease diagnosis and treatment.
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Dysfunctions of miRNAs are frequently found in lung cancer. These noncoding RNAs have been recognized as some of the main regulatory gatekeepers of coding genes in the human genome.
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Owing to their high stability during storage and handling, miRNAs are optimal biomarkers presenting in blood, urine, and other body fluids.
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Early detection is a key to improve the survival of patients with lung cancer. Recent studies have suggested that circulating miRNAs may become promising biomarkers for risk assessment and diagnosis of lung cancer in blood and sputum.
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Some single nucleotide polymorphisms (SNPs) are significantly associated with an increased risk of nonsmall cell lung cancer (NSCLC) and its prognosis.
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Identification of specific miRNAs may provide accurate subclassification of NSCLC.
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Recent studies have demonstrated that miRNAs may serve as predictive biomarkers for the chemoresistance of lung cancer among patients treated with systemic chemotherapy and/or targeted therapies.
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Large prospective cohort studies and cross-validation are needed to consolidate the significant findings demonstrated by studies of miRNA profiling.
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In conjunction with genetic and proteomic signatures and other screening approaches, miRNA biomarkers may represent a new milestone in lung cancer theranostics.
miRNAs are a class of evolutionarily conserved, endogenous, small noncoding RNAs of about 21 to 23 nucleotides in length that participate in diverse biologic pathways and function as posttranscriptional gene regulators during tumorigenesis. These small molecules mainly bind imperfectly to the 3ʹ untranslated region (UTR) of target messenger RNAs (mRNAs). They are encoded in the genome and are generally transcribed by RNA polymerase II. miRNAs work via RNA-induced silencing complexes to target mRNAs in a sequence-specific manner, resulting in mRNA deadenylation followed by exonucleolytic decay, mRNA endonucleolytic cleavage, or translational inhibition. Deregulation of miRNAs is associated with epigenetic and genetic alterations, such as aberrant DNA methylation, amplification, deletion, and point mutation. More than 1000 miRNAs exist in the human genome, and each one can potentially regulate hundreds of mRNAs. miRNAs therefore play an important role in many cellular processes, including apoptosis, differentiation, proliferation, and the stress response.
Lung cancer is the leading cause of cancer mortality worldwide, yet few molecular markers are available for risk screening, subclassification, early diagnosis, survival prognosis, and prediction of treatment response. Researchers have suggested that aberrant miRNA expression profiles may act as oncogenes or tumor suppressors in many types of cancer, including lung cancer. The biologic roles of miRNAs in lung cancer indicate a correlation with disease status, prognosis, and therapeutic outcome. The discovery of miRNAs has opened a new avenue for individualized disease diagnosis and treatment.
The Importance of Micrornas in Lung Cancer
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