Abstract
Simple SummaryFusion of exons or introns from two different genes can lead to the formation of chimeric RNAs. Several recent studies have reported that chimeric RNAs promote tumorigenesis and cancer drug resistance. Therefore, chimeric RNAs are crucial for generating phenotypic diversity between cancer cells that drives the adaptive evolution of cancer. Here, we will discuss the significance of chimeric RNAs in generating functional diversity in cancer cells and their potential impact on developing cancer from an evolutionary viewpoint.Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis. Due to their recurrence in cancers and functional association with oncogenic processes, chimeric RNAs are considered biomarkers for cancer diagnosis. Several recent studies demonstrated that chimeric RNAs could lead to the generation of new functionality for the resistance of cancer cells against drug therapy. Therefore, targeting chimeric RNAs in drug resistance cancer could be useful for developing precision medicine. So, understanding the functional impact of chimeric RNAs in cancer cells from an evolutionary perspective will be helpful to elucidate cancer evolution, which could provide a new insight to design more effective therapies for cancer patients in a personalized manner.
Highlights
Traditionally, cancer development has been accepted as a multistage process driven by the stepwise accumulation of new genetic changes, which promotes the gaining of several abilities that allow cancer cells to survive and proliferate without being subjected to cellular regulatory barriers [1,2,3]
Genomic instability is an important mechanism that enables the acquisition of new characteristics required for oncogenesis, which is the potential driver of cancer evolution [16]
Chimeric RNAs could be generated at the beginning of tumor development due to genomic instability that can sometimes generate novel functionality in cancer cells, enabling them to resist specific drugs before they are ever exposed (Figure 2a), by which some drug treatments might not work for cancer patients
Summary
Cancer development has been accepted as a multistage process driven by the stepwise accumulation of new genetic changes, which promotes the gaining of several abilities that allow cancer cells to survive and proliferate without being subjected to cellular regulatory barriers [1,2,3]. Chimeric RNAs could be translated and generate new fusion or chimeric proteins that could alter the normal pathways and lead to cancer development [19,23,24]. Genomic instability can induce chromosomal aberrations such as translocation, enabling the generation of fusion genes, transcribe them to corresponding chimeric RNAs (Figure 1) [27].
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