Chapters authored
Long Noncoding Mitochondrial RNAs (LncmtRNAs) as Targets for Cancer Therapy
Mitochondria are traditionally been viewed as the cell’s powerhouse, generating most of its ATP. However, besides this fundamental metabolic role, mitochondria are implicated in diverse other processes, including apoptosis, inflammation and metastasis. These functions are exerted in part by the growing class of long noncoding mitochondrial RNAs (lncmtRNAs). We found that normal human proliferating cells express a family of noncoding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA). However, tumor cells express only sense transcripts, suggesting that ASncmtRNA downregulation as a cancer new hallmark. The few ASncmtRNAs copies in tumor cells seem essential to tumor cell viability: knockdown of these transcripts with antisense oligonucleotides (ASO) causes massive apoptotic death of tumor cells, preceded by cell cycle arrest. Preclinical assays show that systemic administration of ASO delayed tumor growth in melanoma and renal cancer models and, caused total remission in subcutaneous renal cancer tumors. The same treatment, however, does not affect normal tissue, suggesting this approach for the development of an efficient and safe therapeutic strategy for several cancer types.
Part of the book: Mitochondrial DNA
Long Non-Coding Mitochondrial RNAs as Novel Molecular Target for Bladder Cancer Treatment
Bladder cancer (BC) is the sixth most common cause of cancer; BC risk increases with age and is more common among men than women. Upon diagnosis, the 5-year relative survival rate for patients is approximately 77%. The treatment options available for bladder cancer include chemotherapy, radiation therapy, immunotherapy, targeted therapy, and surgery. Despite the advances in therapeutically novel approaches, BC remains an important problem of public health. Long non-coding RNA (lncRNA) is defined as non-protein-coding RNA molecule longer than 200 nucleotides. Recent findings have highlighted that lncRNA contributes to the regulation of multiple signaling pathways in bladder cancer, suggesting that lncRNA exerts its roles during the biological processes of tumorigenesis, tumor proliferation, differentiation, apoptosis, invasion, migration, and stemness. In our laboratory, we described a family of mitochondrial long non-coding RNAs containing stem-loop structures, named sense and antisense. These transcripts are found outside the organelle, in the cytosol and nucleus in normal and tumor cells, and are differentially expressed according to proliferative status of cells. The antisense transcript seems to be a novel target for BC treatment based in modified antisense oligonucleotides. In this chapter, the novel biology and role of these RNAs as therapeutical targets will be discussed.
Part of the book: Update on Bladder Cancer