Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer

Abstract

Cervical cancer is one of the most common malignancies in women in terms of prevalence and mortality. Cervical cancer has some particularities that distinguish it from any other oncologic pathology: first, it is completely preventable by prompt detection of its precursor, cervical intraepithelial neoplasia (CIN); second, the Human Papillomavirus (HPV) infection is a known etiological agent; third, the mean age at diagnosis is much lower than in other oncologic conditions, as a consequence of the sexually-transmitted HPV. Methods: We evaluated the expression level of several long noncoding RNAs and a microRNA in samples from 30 patients with CIN, 9 with cervical cancer and 38 normal samples using qRT-PCR technology. Results: We observed higher expression levels for MEG3, DAPK1, MLH1 and MALAT1 in CIN samples than in normal samples, whereas TIMP3 and SOX1 had lower expression levels. For cancer samples, DAPK1, MLH1 and MALAT1 had higher expression, and MEG3, TIMP3 and SOX1 had lower expression when compared to normal samples. In the case of CIN versus cancer samples, only MEG3 gene showed a statistically significant difference. The expression of miR-205-5p was lower in both CIN and cancer samples compared to normal samples. Conclusion: Decreased MEG3 expression could be considered an alarm signal in the transition from a premalignant cervical lesion to invasive cancer, while altered expression levels of TIMP3, SOX1, MLH1, MALAT1 and miR-205-5p could serve as early biomarkers in the diagnosis of premalignant cervical lesions. Future studies, including a larger number of patients with CIN, will be of particular importance in validating these observations.

Oncogenic HPV-induced high expression of ESM1 predicts poor prognosis and regulates aerobic glycolysis in cervical cancer

“…The decreased expression of miR-205-5p was observed in both CIN and cancer samples compared to normal samples, which may serve as an early biomarker in the diagnosis of premalignant cervical lesions. 25 Through miR-205-5p inhibitor or mimic transfection and dual luciferase reporter assays, we confirmed that ESM1 is a target of ESM1 in cervical cancer.…”

Expression of collagenases (matrix metalloproteinase-1, -8, -13) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in naturally occurring bovine cutaneous fibropapillomas

“…Reduced protein expression of TIMP-3 was associated with reduced tumor differentiation and increased metastatic activity, since its binding to MMPs in tumor cells is leading to a reduced ECM-degrading activity ( 38 ). Moreover, a decreased expression of TIMP-3 has been reported in cervical intraepithelial neoplasia and cervical cancer related to HPV, which in turn may be responsible implicitly by an impaired extracellular matrix degradation activity and cyto-architectural abnormalities ( 39 ). In our study, in fibropapillomas, a weak to moderate expression was noted by immunohistochemistry mostly in the upper epithelial layers, and next, by western blot analysis, a down-regulated expression was confirmed, which may support an important contribution in impairing the collagenases activity.…”

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology

“…Some studies have indicated that the expression level of TIMP3 is lower in cervical intraepithelial neoplasia and cancer tissues than in normal samples [ 131 , 132 , 133 , 134 ] ( Table 4 ). According to the TCGA data, TIMP3 expression is lower in cancer samples than in normal samples [ 131 ].…”

“…Some studies have indicated that the expression level of TIMP3 is lower in cervical intraepithelial neoplasia and cancer tissues than in normal samples [ 131 , 132 , 133 , 134 ] ( Table 4 ). According to the TCGA data, TIMP3 expression is lower in cancer samples than in normal samples [ 131 ]. Compared to patients with lower expression levels of TIMP3 in cervical cancer tissues, those with higher TIMP3 expression correlate with a lower survival rate; however, no significance has been observed [ 131 ].…”

“…According to the TCGA data, TIMP3 expression is lower in cancer samples than in normal samples [ 131 ]. Compared to patients with lower expression levels of TIMP3 in cervical cancer tissues, those with higher TIMP3 expression correlate with a lower survival rate; however, no significance has been observed [ 131 ].…”