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Sequence Variations of MicroRNAs in Human Cancer: Alterations in Predicted Secondary Structure Do Not Affect Processing

Diederichs, Sven, Haber, Daniel A.·2006·Cancer Research

Abstract

Expression levels of microRNAs (miRNAs) are globally reduced in cancer compared with matched normal tissues, and miRNA function has recently been implicated in tumorigenesis. To test whether epigenetic silencing contributes to miRNA suppression in tumors, lung cancer cells were treated with inhibitors of DNA methylation or histone deacetylation. No significant alteration in miRNA expression was detected using microarray profiling. To search for tumor-associated mutations that could affect processing and expression of mature miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence variations in 15 miRNAs implicated in tumorigenesis by virtue of their known target transcripts (let-7 family targeting oncogenic Ras) or their localization to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and miR-21). No mutations were detected within any of the short mature miRNA sequences. In addition to previously reported polymorphisms, 1 sequence variant in a precursor miRNA and 15 variants in primary miRNA (pri-miRNA) transcripts were identified. Despite pri-miRNAs having dramatic changes in the predicted secondary folding structure flanking putative cleavage sites, processing and miRNA maturation were not affected in vivo. Thus, genetic variants in miRNA precursors are common in cancer cells but are unlikely to have physiologic significance. (Cancer Res 2006; 66(12): 6097-104)

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Metadata

Authors
Diederichs, S., & Haber, D. A.
Venue
Cancer Research
Published
2006-06-15
Volume
66
Issue
12
Pages
6097-6104
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2141915880
Cited by
176
References
6
FWCI
7.55
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Sequence Variations of MicroRNAs in Human Cancer: Alterations in Predicted Secondary Structure Do Not Affect Processing. https://app.cochat.ai/papers/10.1158/0008-5472.can-06-0537
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Diederichs, S., & Haber, D. A. (2006). Sequence Variations of MicroRNAs in Human Cancer: Alterations in Predicted Secondary Structure Do Not Affect Processing. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-0537

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