Abstract
Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC.
Highlights
MicroRNAs are endogenous, short (19–24 nucleotides) non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 31-untranslated regions of protein-coding transcripts [1,2]. miRNAs have been exhaustively studied due to their role in embryonic development [1,3]
Results from the Dunn multiple comparisons test suggested that the differences that occurred between groups were due to the high DNA repair capacity (DRC) levels of breast cancer (BC) patients
Our main objective was to examine the expression of Let-7b in BC patients versus a control group of women without BC using their DRC levels measured in lymphocytes as the basis for our analysis
Summary
MicroRNAs (miRNAs) are endogenous, short (19–24 nucleotides) non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 31-untranslated regions of protein-coding transcripts [1,2]. miRNAs have been exhaustively studied due to their role in embryonic development [1,3]. The NER pathway is the most complex DNA repair pathway and includes the repair of bulky, helix-distorting DNA lesions, such as those induced by crosslinking agents and base-damaging carcinogens and chemical mutagens [12,13,16] Defects in this pathway are normally associated with rare genetic syndromes and cancers [18] (e.g., Xeroderma pigmentosum (XP) and Cockayne syndrome). There are no studies on the association between DRC levels and Let-7b expression in BC This miRNA family has been widely studied, only a few articles have reported different types of Let-7b regulation, in BC [2,4,5,9,10]. We studied the expression of Let-7b in plasma of 73 BC patients and in 72 women without BC, with either high or low DRC levels. DRC was measured in human lymphocytes with different severities of NER deficiency by means of a host-cell reactivation phenotypic assay with a luciferase reporter gene [15]
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