Expression of Mir-21 and Mir-143 in Cervical Specimens Ranging from Histologically Normal through to Invasive Cervical Cancer

Abstract

BackgroundMicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples.Methodology/Principal FindingsWe measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervical cancer cell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2–3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target.ConclusionsWhilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervical cancer.

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer

“…Local and systemic metastasis is a major cause leading to a dismal prognosis of CC. Increasing evidence has confirmed miRNAs as key regulators in the metastasis of various types of cancer, including CC (27). In the present study, we found that miR-1297 was significantly downregulated in CC tissues compared with the corresponding non-cancerous tissues.…”

microRNA Portraits in Human Vulvar Carcinoma

“…Nuovo et al 2010 (5) have shown a strong inverse correlation between this microRNA and HPV DNA in productive infection in cervical cancer. Other microRNAs observed in our study, such as microRNA-21, have also been identified as significantly deregulated in a range of cancers, including cervical cancer (26). miR-16 seems to be important within HPV pathogenesis in head and neck squamous cell carcinomas (27).…”

Expressions and clinic significance of miRNA-143, miRNA- 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer tissues

“…A number of studies have identified miRNA-143 as a tumor suppressor gene lost expression significantly in several cancer types, including breast and cervical cancers [10][11][12][13], which is consistent with our results on the expression of miRNA-143 in cervical cancer tissues. miRNA-143 was expressed at significantly lower levels when compared to the normal control tissues.…”