RESUMO
Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.
Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , Transição Epitelial-Mesenquimal , RNA Longo não Codificante/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/radioterapia , Fator de Crescimento Transformador beta/metabolismo , Fatores de Transcrição/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Cancer is a challenging to treat disease with a high mortality rate worldwide, nevertheless advances in science has led to a decrease in the number of death cases caused by cancer. Aberrant expression of genes occurs during tumorigenesis therefore targeting the signaling pathways that regulate these genes' expression is of importance in cancer therapy. Notch is one of the signaling pathways having interactions with other vital cell signaling molecules responsible for cellular functions such as proliferation, apoptosis, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune evasion. Furthermore, the Notch pathway is involved in response to chemo- and radiotherapy. Thus, targeting the Notch signaling pathway in cancer therapy can be beneficial for overcoming the therapeutic gaps. Non-coding RNAs (ncRNAs) are a class of RNAs that include short ncRNAs (such as micro RNAs) and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are ~22 nucleotides in length while lncRNAs have more than 200 nucleotides. Both miRNAs and lncRNAs control vital cellular mechanisms in cells and affect various signaling pathways and Notch is among them. The current review aims to discuss the critical role of ncRNAs in the regulation of the Notch signaling pathway by focusing on different cancer hallmarks including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.
