Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in t...Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in the pathogenesis of various diseases.CircRNAs are highly stable and usually expressed in a tissue-or cell type-specific manner.Therefore,they are currently being explored as potential therapeutic targets.Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies,respectively.These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems.Furthermore,recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner.While still in the early stages of development,the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency.In this review,we describe circRNA properties and functions and highlight their significance in disease.We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach.Lastly,we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.展开更多
Main text Colon cancer,one of the most common cancers in the world[1]and China[2,3],is typically diagnosed in its advanced stages.However,only a mediocre 20%-30%of these patients can have curative resection,but still,...Main text Colon cancer,one of the most common cancers in the world[1]and China[2,3],is typically diagnosed in its advanced stages.However,only a mediocre 20%-30%of these patients can have curative resection,but still,they are at high risk of recurrent disease[4].Given that recur-rent disease is especially associated with poor outcomes,optimizing the therapeutic strategy is paramount.Adju-vant chemotherapy,a standard treatment for stage II/III colon cancer,is often accompanied by a significant increase in survival[5,6].Thus,timely adjuvant therapy is primordial for reducing postoperative recurrence risk.To assess the risk of postoperative recurrence,biomark-ers of greater prognostic essence than traditional clin-icopathology are urgently needed.The emerging role of circular RNAs(circRNAs),a newly discovered type of regulatory RNAs,has shed light on whether these mol-ecules can serve as biomarkers for predicting the post-operative recurrence of colon cancer.circRNAs are characterized by a covalently closed loop that is capa-ble of regulating gene expression at the transcriptional or post-transcriptional levels[7].They can also bind to proteins and thereby regulate the intracellular signaling pathways[8,9].Recent reports have described the roles of circRNAs in the initiation and progression of cancer[10-12],and increasing evidence have demonstrated that circRNAs may serve as molecular biomarkers to facili-tate diagnostic and prognostic evaluations[13].However,the potential of circRNAs for diagnosing and prognosing colon cancer is less clear.展开更多
基金supported by grants from Canadian Institutes of Health Research to BBY(PJT-153105,PJT-155962,and PJT-166107).
文摘Significant progress has been made in circular RNA(circRNA)research in recent years.Increasing evidence suggests that circRNAs play important roles in many cellular processes,and their dysregulation is implicated in the pathogenesis of various diseases.CircRNAs are highly stable and usually expressed in a tissue-or cell type-specific manner.Therefore,they are currently being explored as potential therapeutic targets.Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies,respectively.These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems.Furthermore,recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner.While still in the early stages of development,the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency.In this review,we describe circRNA properties and functions and highlight their significance in disease.We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach.Lastly,we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.
文摘Main text Colon cancer,one of the most common cancers in the world[1]and China[2,3],is typically diagnosed in its advanced stages.However,only a mediocre 20%-30%of these patients can have curative resection,but still,they are at high risk of recurrent disease[4].Given that recur-rent disease is especially associated with poor outcomes,optimizing the therapeutic strategy is paramount.Adju-vant chemotherapy,a standard treatment for stage II/III colon cancer,is often accompanied by a significant increase in survival[5,6].Thus,timely adjuvant therapy is primordial for reducing postoperative recurrence risk.To assess the risk of postoperative recurrence,biomark-ers of greater prognostic essence than traditional clin-icopathology are urgently needed.The emerging role of circular RNAs(circRNAs),a newly discovered type of regulatory RNAs,has shed light on whether these mol-ecules can serve as biomarkers for predicting the post-operative recurrence of colon cancer.circRNAs are characterized by a covalently closed loop that is capa-ble of regulating gene expression at the transcriptional or post-transcriptional levels[7].They can also bind to proteins and thereby regulate the intracellular signaling pathways[8,9].Recent reports have described the roles of circRNAs in the initiation and progression of cancer[10-12],and increasing evidence have demonstrated that circRNAs may serve as molecular biomarkers to facili-tate diagnostic and prognostic evaluations[13].However,the potential of circRNAs for diagnosing and prognosing colon cancer is less clear.
