نقش سیرتوئین ها در مقاومت دارویی به سرطان
Abstract
1- Introduction
2- Noncoding RNAs and sirtuins function in cancer drug resistance
3- Future prospective and conclusion
References
Abstract
Cancer is a rising and major health issue around the world. The acquisition of resistance to chemotherapeutic drugs is a great obstacle for the effective treatment of nearly all cancers. Drug resistance is regulated by multiple factors and mechanisms including genetic mutations, abnormal expression of some cellular transporters such as multidrug resistance (MDR) transporters, changes in apoptotic pathways, cancer stem cells, tumor microenvironment, and noncoding RNAs (ncRNAs). Evidence clearly indicates a key role for sirtuins in several characteristics of cancer drug resistance. Recent studies demonstrated the crucial impact of some ncRNAs on sirtuins expression leading to modulation of chemotherapy resistance in cancers. In this review, we will focus on the current findings about the impacts of ncRNAs on the sirtuins pathway and their role in drug resistance of cancer.
Introduction
Cancer is considered a complex disease associated with some genetic mutations, deletions, epigenetic alterations and chromosomal translocations that are involved in cancer initiation, promotion, metastasis and drug resistance (Bach and Lee, 2018). Chemotherapy is one of the most widely used therapies for the treatment of cancer and improves the lifespan of patients. However, prolonged utilization of chemotherapeutic drugs. may lead to drug resistance which is a major issue in cancer treatment (Szakacs et al., 2006). Based on statistical reports, over than 90% of deaths in patients with different types of cancer are associated with chemotherapeutic drug resistance (Li et al., 2008; Longley and Johnston, 2005). Cancer cells apply many different mechanisms to impede drug treatment, including the genetic mutations, cell cycle alterations, apoptosis induction, drug metabolism, efflux alterations and DNA methylation (Balch et al., 2004; Gillet and Gottesman, 2010; Xia and Hui, 2014). NcRNAs have been reported to play an essential role in determining drug sensitivity or restoring drug sensitivity in resistant cells in many cancers. (Kapranov et al., 2010). NcRNAs are RNA molecules that do not code any protein. However, they exert an important impact on the expression of more than 60% of human genes. They are classified into two main groups including the most studied microRNAs (miRNAs) and the long non-coding RNAs (lncRNA) (Kapranov et al., 2010). MiRNAs are single-stranded RNAs, 19-23bp in length and account for approximately 30% of gene expression regulation. MiRNAs can bind to the 3′ untranslated regions (UTRs) of their target mRNAs and regulate gene expression. The most important function of miRNAs is the suppression of gene expression (Omidkhoda et al., 2019; Szulwach et al., 2010). lncRNAs are transcripts with 200 nt to ~100 kb in length. They do not have any significant open reading frames. lncRNAs are poly-adenylated and located within the cell nucleus or cytosol. They can regulate the expression of genes by cis-acting or trans-acting regulation. Cis-acting lncRNAs affect the expression of neighboring genes by acting at the site of transcription, while trans-acting lncRNAs affect the expression of genes by acting away from the site of synthesis (Barangi et al., 2019; Batista and Chang, 2013).