Hsa-miR-193-3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura.
Reintroduction of miR-200c into highly invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation.
In addition, miR-200c overexpression significantly inhibited melanoma xenograft growth and metastasis in vivo, and this correlated with diminished expression of BMI-1 and reduced levels of E-cadherin in these tumors.
Since survival upon detachment from basement membrane is required for metastasis, the ability to resist anoikis contributes to the metastatic potential of breast tumors. miR-200c, a potent repressor of epithelial to mesenchymal transition, is expressed in luminal breast cancers, but is lost in more aggressive basal-like, or triple negative breast cancers (TNBC).
Taken together, our study demonstrated that miR-200c inhibits metastatic ability by targeting ZEB1 in colon cancer cells SW480/620 and suggested that modulation of miR-200c could serve as therapeutic tool for inhibiting metastasis in colorectal cancer.
Here, we demonstrate by ectopic expression and gene silencing that the proto-oncogene c-Myb activates the expression of the 5 members of miR200 family (miR200b, miR200a, miR429, miR200c and miR141) that are involved in the control of epithelial-mesenchymal transition (EMT) and metastasis in many types of cancers.
It has been reported that microRNA-200c (miRNA-200c), a non-coding RNA, is important in the epithelial to mesenchymal transition (EMT) and metastasis in breast cancer cells.
The aim of the present study was to investigate the possible roles of miR-200c in regulating metastasis and to identify its target genes in renal cell carcinoma (RCC).
Therefore, our study unraveled nested regulatory circuits of miR-200c/ZEB1 and miR-200c/ZNF217/TGF-β/ZEB1 in synergistically promoting trastuzumab resistance and metastasis of breast cancer cells.
This study was to investigate the effect of miR-200c on regulation of ovarian cancer cell metastasis potential and explore the underlying molecular events. qRT-PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and 30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c expression in ovarian cancer cells for detection of changed phenotypes of tumor cells.
In PR-negative cases, high miR-200c expression was associated with shortened relapse-free survival (Cox regression: P = 0.001, OR = 3.613); increased local/distant recurrence (Logistic regression: P = 0.006, OR = 3.965); and more frequent distant metastasis (Logistic regression: P = 0.015, OR = 3.390).
Moreover, in clinicopathology analysis, miR-200c expression in blood was significantly associated with TNM stage, lymph node metastasis and distant metastasis.
The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET).
Integrated analyses allow understanding the interplay between different levels of molecular alterations.We integrated miRNA and gene expression data from 458 ccRCC and 254 normal kidney specimens to construct a miRNA-target interaction network.We identified the downregulated miR-124-3p, -30a-5p and -200c-3p as the most influential miRNAs in RCC pathogenesis.miR-124-3p and miR-200c-3p expression showed association with patient survival, miR-30a-5p was downregulated in metastases compared to primary tumors.
In the last two decades, identification of almost 2600 miRNAs in human and their potential to be modulated opened a new avenue to target almost all hallmarks of cancer. miRNAs have been classified as tumor suppressors or oncogenes depending on the phenotype they induce, the targets they modulate, and the tissue where they function. miR-200c, an illustrious tumor suppressor, is one of the highly studied miRNAs in terms of development, stemness, proliferation, epithelial-mesenchymal transition (EMT), therapy resistance, and metastasis.
miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC).