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. Keywords TNBC. miRNA. Cancer biomarkers. miRNA-based therapy Abbreviations Bmi 1 B lymphoma Mo-MLV insertion region 1 homolog CSC Cancer stem cells ER Estrogen receptor HER 2 Human epidermal growth factor receptor 2 PR Progesterone receptor TNBC Triple-negative breast cancer ts-microRNA Tumor suppressor microRNA Highlights • Patients diagnosed with negative ER, PR, and HER 2 are the most prevalent subtypes of breast cancer with limited targeted therapy. • miRNAs play a key role in regulating the gene expression of the key biological processes including proliferation, differentiation, angiogenesis, migration, and apoptosis. The involvement of miRNA has also been identified in carcinogenesis. • In TNBC, miRNAs make major contributions to the diagnosis, prognosis, and treatment. • We suggest that miRNA-based therapeutics could be a promising approach in the treatment of TNBC.
: Alzheimer’s disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of the existence, which is getting worse for the human brain, is necessary to taken care of the all critical measures. The disease causes due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach and provides a hope for the new drugs for AD, which is summarized herein with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient to provide a list of chemical ingredients of the plant to cure the AD and screened them against the various potential targets of the AD. The synthesis of a highly functionalized scaffold in one step in one pot without isolating the intermediate is a challenging task, but in a few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. The multi-component is widely accepted technique by the drug discovery people due to its high atom economy and it reduces multi-step process to a one-step process, so, the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring to the importance of the fast as well as a smart synthesis of the bio-relevant molecules.
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.
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