Metastasis and resistance to therapy significantly contribute to cancer-related deaths. Growing body of evidence suggest that altered expression of microRNAs (miRNAs) is one of the root cause of adverse clinical outcome. miRNAs such as let-7 are the new fine tuners of signaling cascade and cellular processes which regulates the genes in post-transcriptional manner. In this review, we described the regulation of let-7 expression and the involvement of molecular factors in this process. We discussed the mechanism by which let-7 alter the expression of genes involved in the process of tumorigenesis. Further, we listed the pathways targeted by let-7 to reduce the burden of the tumor. In addition, we described the role of let-7 in breast cancer metastasis and stemness properties. This article will provide the in-depth insight into the biology of let-7 miRNA and its role in the breast cancer progression.
OBJECTIVE
The clinical utility of TRAIL in the treatment of established human malignancies is limited by the development of resistance to TRAIL. We hypothesized that knockdown of MADD, a TRAIL-resistance factor, may overcome TRAIL resistance in ovarian cancer cells.
STUDY DESIGN
MADD expression in resected ovarian cancer specimens and cell lines was quantified using q-RT-PCR. Sensitivity of ovarian cancer cell lines to TRAIL, with or without MADD knockdown was assessed.
RESULTS
MADD is expressed at relatively higher levels in human malignant ovarian cancer tissues and cell lines compared to normal ovarian tissues. The cell lines OVCA429 and OVCAR3 were susceptible, and CAOV-3 and SKOV-3 were resistant to TRAIL. MADD knockdown in CAOV-3 cells, but not in SKOV-3 cells, conferred TRAIL sensitivity. Knockdown of c-FLIP in SKOV-3 cells increased spontaneous and TRAIL-induced apoptosis, which was further increased upon MADD knockdown.
CONCLUSION
MADD/c-FLIPL knockdown can render TRAIL-resistant ovarian cancer cells susceptible to TRAIL.
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