Altered microRNA expression associated with chromosomal changes contributes to cervical carcinogenesis

Abstract

Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability. In this study, miRNA expression in normal cervical squamous epithelium, high-grade precancerous lesions (cervical intraepithelial neoplasia (CIN2-3)), squamous cell carcinomas (SCCs) and adenocarcinomas (AdCAs) was integrated with previously generated chromosomal profiles of the same samples. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Of these differentially expressed miRNAs, 27 showed early transiently altered expression in CIN2-3 lesions only, 46 miRNAs showed late altered expression in SCCs only and 33 showed continuously altered expression in both CIN2-3 and SCCs. Altered expression of five significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1), was directly linked to frequent chromosomal alterations. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain of 1q. Hsa-miR-9 overexpression was found to increase cell viability, anchorage-independent growth and migration in vitro. Upon organic raft culturing, hsa-miR-9 hampered differentiation and induced proliferation in all strata of the epithelial layer. These findings support a potential oncogenic function of hsa-miR-9 in cervical cancer. In summary, differential expression of 106 miRNAs, partly associated with chromosomal alterations, was observed during cervical SCC development. Altered expression of hsa-miR-9 associated with a chromosomal gain of chromosome 1q was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis.

microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

“…Deregulated miR-28 expression has been observed in several types of cancer, including up-regulation in esophageal, cervical, and renal cancer, and in myeloproliferative malignancies and down-regulation in colorectal cancer and nasal-type natural killer/T-cell lymphoma (10)(11)(12)(13)(14)(15)(16). These apparently inconsistent observations are not surprising because it is well established that miRNAs can act both as tumor suppressors and oncogenes depending on the cell context (29).…”

“…miR-28 has been shown to be deregulated in several cancer types. Although increased levels of miR-28 expression have been observed in esophageal, cervical, renal cancer, as well as in the platelets of a fraction of myeloproliferative neoplasm patients (10)(11)(12)(13), miR-28 is down-regulated in colorectal cancer cells and nasal-type natural killer/T-cell lymphoma. In both these latter cell types, reexpression of miR-28 leads to reduced proliferation in cell lines (14)(15)(16).…”

Serum miR-9 as a prognostic biomarker in patients with osteosarcoma

“…[19][20][21] Altered miR-9 expression is associated with the development and progression of cancers, [22][23][24][25] Kaplan-Meier analysis of overall survival in patients with osteosarcoma, stratified according to median serum microRNA-9 (miR-9) concentration (expression). The colour version of this figure is available at: http://imr.sagepub.com nonsmall-cell lung cancer 16 ) highly expressed miR-9 promotes cancer-cell growth and/or metastasis.…”

Les multiples facettes d’un petit régulateur

“…Dans certains cas, miR-9 présente des propriétés oncogéniques (favorisant la progression tumorale), alors que dans d'autres, il se comporte comme un gène suppresseur de tumeurs (agissant contre la progression tumorale). Ainsi, miR-9 est fortement exprimé et participe au développement de lymphomes de Hodgkin [37], ou de certains cancers du sein [38], du col de l'utérus [39], du côlon [40] et de l'estomac [41]. Cette implication de miR-9 dans des cancers de tissus si variés est le signe que l'expression de miR-9 peut être associée à des états ou processus cellulaires généraux et non spécifiques des tissus neuraux.…”