Recent developments in targeting genes and pathways by RNAi‐based approaches in colorectal cancer

Abstract

A wide spectrum of genetic and epigenetic variations together with environmental factors has made colorectal cancer (CRC), which involves the colon and rectum, a challenging and heterogeneous cancer. CRC cannot be effectively overcomed by common conventional therapies including surgery, chemotherapy, targeted therapy, and hormone replacement which highlights the need for a rational design of novel anticancer therapy. Accumulating evidence indicates that RNA interference (RNAi) could be an important avenue to generate great therapeutic efficacy for CRC by targeting genes that are responsible for the viability, cell cycle, proliferation, apoptosis, differentiation, metastasis, and invasion of CRC cells. In this review, we underline the documented benefits of small interfering RNAs and short hairpin RNAs to target genes and signaling pathways related to CRC tumorigenesis. We address the synergistic effects of RNAi‐mediated gene knockdown and inhibitors/chemotherapy agents to increase the sensitivity of CRC cells to common therapies. Finally, this review points new delivery systems/materials for improving the cellular uptake efficiency and reducing off‐target effects of RNAi.

CtDNA’s prognostic value in patients with early-stage colorectal cancer after surgery: A meta-analysis and systematic review

“…The main pathways involved in colorectal cancer development are the adenoma-carcinoma pathway and the serrated pathway, which involve multiple genetic mutations, such as those in MMR genes, APC, and KRAS. [ 27 ] Colorectal cancer is heterogeneous, and even patients at the same stage may have a very different prognosis due to different genetic mutations involved. [ 4 , 21 ] While it may appear challenging to identify all cancerous genes, the presence of small residual tumors can be detected by examining the ctDNA of these mutated genes.…”

ErbB3-Targeting Oncolytic Adenovirus Causes Potent Tumor Suppression by Induction of Apoptosis in Cancer Cells

“…However, the major limitation of RNAi is that it is difficult to efficiently deliver them to target tissues and has a possibility of an off-target effect [44]. Accordingly, a variety of new viral and nonviral delivery systems have been introduced for improving the cellular uptake efficiency and reducing the off-target effects of RNAi [45].…”

The various regulatory functions of long noncoding RNAs in apoptosis, cell cycle, and cellular senescence

“…Downregulation of TUG1 in some cancers such as brain tumor (glioma) and non‐small cell lung carcinoma (NSCLC) causes an increase in tumor size and a decrease in overall survival, suggesting its activity as a tumor suppressor 34,35,99 . The evidence is provided through a reduction in apoptosis levels mediated by TUG1 knockdown via siRNA, 34,99 as a knockdown agency 100 . Besides, overexpression of TUG1 using TUG1‐pcDNA transfer in cancerous glioma cells regulates the activation of caspases 3 and 9, inhibition of BCL‐2, and subsequently a higher apoptosis rate 34,99 .…”

“…34,35,99 The evidence is provided through a reduction in apoptosis levels mediated by TUG1 knockdown via siRNA, 34,99 as a knockdown agency. 100 Besides, overexpression of TUG1 using TUG1-pcDNA transfer in cancerous glioma cells regulates the activation of caspases 3 and 9, inhibition of BCL-2, and subsequently a higher apoptosis rate. 34,99 In NSCLC, TUG1 is a direct target of p53 and acts as a growth regulator.…”