Clinical Impact of microRNAs Associated With Cancer Stem Cells as a Prognostic Factor in Ovarian Carcinoma

Abstract

Background: Ovarian carcinoma is a highly lethal gynecological malignancy due to its frequent relapses and adoption of chemoresistance. To develop new biomarkers for disease progression in ovarian carcinoma, CSCs, which are considered to contribute to disease relapse and metastasis, were isolated from human ovarian carcinoma tissues, and differentially expressed microRNAs (miRNAs) in CSCs were identified and assessed the clinical implication of expression of these miRNAs.Methods: Primary cancer cells derived from human ovarian carcinomas were cultured and spheroid-forming cells (SFCs) were isolated. Profiles of miRNA expression in CSC-like SFCs were identified by miRNA microarray and the results were validated by quantitative real-time RT-PCR (qRT-PCR). We also assessed the correlations between miRNA expression levels and clinicopathological parameters in ovarian carcinomas.Results: Five miRNAs (miR-5703, miR-630, miR-1246, miR-424-5p, and miR-320b) were significantly dysregulated in CSC-like SFCs compared with primary cancer cells. The qRT-PCR showed that miR-5703 and miR-1246 expression was significantly higher in ovarian cancer cells than in normal control cells, whereas the miR-424-5p level was significantly lower. Decreased expression of miR-424-5p was significantly associated with distant metastasis in high stage (stage IIII & IV) carcinomas (35.5% vs. 72.2%, respectively, p=0.013)Conclusion: Taken together, miR-5703, miR-630, miR-1246, miR-424-5p, and miR-320b are useful markers for enriching ovarian CSCs. Decreased expression of miR-424-5p in ovarian carcinoma might be a putative biomarker for distant metastasis in ovarian carcinoma.

The Epigenetic Landscape of Pancreatic Cancer Stem Cells

“…In the last 10 years, miRNAs have also provided new insights into gene regulation implicated in tumorigenesis and CSC biology [104]. Several miRNAs involved in CSC biology in different solid tumors have been identified: (i) miR-5703, miR-630, miR-1246, miR-424-5p and miR-320b were all deregulated in ovarian CSCs [105]; (ii) miR-34a, miR-200b/c, miR-203 and miR-137 appear to be critical in CRC CSCs [106]; (iii) the miR-200 family and miR-let7 family are crucial for CSC dynamics in breast cancer [107]; (iv) miR181-5p, miR153 and the miR17-92 cluster are relevant for the pancreatic CSC sub-population [45,108,109]. Remarkably, secreted exosomes from CSCs also orchestrate autocrine and paracrine functions, which alter the tumor microenvironment, as well as the growth and progression of the tumor.…”

Relationship between ovarian cancer stem cells, epithelial mesenchymal transition and tumour recurrence

“…In particular, miR-424-5p was linked to distant metastasis, suggesting a role in dissemination of disease [55] . Given that miRNAs control CSC self-renewal and differentiation, these findings suggest that miR-424-5p is a potential biomarker for poor prognosis in OC, making this an attractive target in terms of therapeutics.…”

MicroRNA‐424‐5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3‐mediated nuclear factor‐κB signalling pathway

“…In recent years, numerous microRNAs (miRs or miRNAs) have been identified as important biomarkers in the initiation and progression of AS (Andreou, Sun, Stone, Edelman, & Feinberg, ). miR‐424‐5p is located on human chromosome Xq26.3, and has been recently classified in a large cluster, along with miR‐15/miR‐16 (Wang, Wang, Yang, Chen, & Wang, ), that has been reported to be involved in the progression of various cancers, including breast cancer, pancreatic cancer and ovarian cancer (Cha, Choi, Hwang, Jeong, & An, ; Liu et al., ; Wang, Wang, Zhou, & Qian, ; Wu et al., ). Moreover, miR‐424‐5p also plays a role in chronic obstructive pulmonary disease by targeting a number of proteins involved in protein synthesis or in the inhibition of catabolic processes (Connolly et al., ).…”