Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers.

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5' and 3'- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

A perspective on the diagnostics, prognostics, and therapeutics of microRNAs of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive and prevalent subtype of breast cancer in women worldwide. Currently, chemotherapy remains the main modality for the treatment at an early stage, as there is no approved targeted therapy for early TNBC. In this review, we investigate the use of microRNAs (miRNAs), which play a key role in the post-transcriptional regulation of genes involved in the key biological processes, namely proliferation, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. Here, we emphasize the importance of the recent advances related to miRNAs, involving diagnosis, prognosis, and treatment of TNBC. We focus on the development, optimization, and stabilization of miRNA-based drugs; improvement of miRNA delivery; and control of the off-target effects of miRNA therapeutics. We speculate as to which features may present themselves as promising approaches in the treatment of TNBC.