Abstract
Cancer statistics in 2018 highlight an 8.6 million incidence in female cancers, and 4.2 million cancer deaths globally. Moreover, breast cancer is the most frequent malignancy in females and twenty percent of these develop metastasis. This provides only a small chance for successful therapy, and identification of new molecular markers for the diagnosis and prognostic prediction of metastatic disease and development of innovative therapeutic molecules are therefore urgently required. Differentially expressed microRNAs (miRNAs) in cancers cause multiple changes in the expression of the tumorigenesis-promoting genes which have mostly been investigated in breast cancers. Herein, we summarize recent data on breast cancer-specific miRNA expression profiles and their participation in regulating invasive processes, in association with changes in cytoskeletal structure, cell-cell adhesion junctions, cancer cell-extracellular matrix interactions, tumor microenvironments, epithelial-to-mesenchymal transitions and cancer cell stem abilities. We then focused on the epigenetic regulation of individual miRNAs and their modified interactions with other regulatory genes, and reviewed the function of miRNA isoforms and exosome-mediated miRNA transfer in cancer invasiveness. Although research into miRNA’s function in cancer is still ongoing, results herein contribute to improved metastatic cancer management.
Highlights
GLOBOCAN 2018 statistical estimates from the International Agency for Research on Cancer reveal almost 8.6 million new female cancer cases and 4.2 million associated deaths
The snail family transcriptional repressor 1 (SNAIL1) protein-dependent activation of epithelial-to-mesenchymal transition (EMT) was observed in p53 loss-of-function cancer cell lines, including breast cancer patients (BC), because of a decrease in the levels of miR-34 which is a direct regulator of SNAI1
The high incidence of female malignancy-associated death, predominantly associated with BC, and the relatively high percentage of metastases highlight the urgent need for knowledge on a deeper molecular level for the following mechanisms: cancer cell detachment from the primary site, dissemination and propagation in secondary organs, and the miRNA regulation of the relevant genes
Summary
GLOBOCAN 2018 statistical estimates from the International Agency for Research on Cancer reveal almost 8.6 million new female cancer cases and 4.2 million associated deaths. Ovarian cancer (OC) has the second highest mortality rate of all gynaecological malignancies and approximately 75% of patients have cancer cell dissemination in the peritoneal cavity at the time of diagnosis [6] These tumors were mostly epithelial and usually primary, but 10–20% were diagnosed as ovarian metastases of breast, colorectal, endometrial, stomach, or appendix cancer [7]. The cancer cells are arrested or adhere to vessel walls and extravasate into the parenchyma of distant organ, where surviving cancer cells form micro-metastases and proliferate into macro-metastases to form a metastatic colonization [10,11] During these processes, cancer cells and non-malignant cells in the tumor microenvironment (TM) undergo genetic and epigenetic changes [12]. For patients with early cancer lesions, an understanding of the mechanisms allowing the physical relocation of cancer cells from primary tumors is likely to be helpful for preventing metastasis, and for patients with metastatic seeding greater knowledge of the mechanisms leading to successful colonization of cancer cells should contribute to the development of more effective therapy [17]
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