• Investigating The Function Of Circular RNA In Diagnosis And Treatment Of Colorectal Cancer
  • Samaneh Dalali,1,* Fatemeh Kaviani,2 Maryam Peymani,3
    1. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
    2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
    3. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran


  • Introduction: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract,is a serious disease characterized as uncontrolled division or abnormal growth of colon or rectum cells. (CRC) is the second most common adult cancer in women and the third most common in men, and it is the fourth leading cause of cancer death.The risk of developing CRC is affected by genetic, epigenetic and environmental factors. Circular RNAs (CircRNAs) is a class of endogenous noncoding RNAs, and are generated from back-splicing events and defined by covalently closed circular configuration without 5’ end caps and 3’ polyadenylated tails. Compared with linear RNAs, CircRNAs are much more stable than linear RNAs (with a half-life beyond 48 h) which have a high degree of stability and potential effect on gene regulation. Among the lncRNAs, circular (circ)RNAs are a group of naturally occurring endogenous ncRNAs having transcript lengths of hundreds to thousands of nucleotides. circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. circRNAs have unique associations with tumour size, staging and overall survival in CRC that lend circRNAs the potential to serve as diagnostic and prognostic biomarkers. We aim to provide insight in the development of therapy and clinical decision-making.
  • Methods: circRNAs as biomarkers for colorectal cancer ; Several circRNAs have been proposed as useful therapeutic targets for CRC. For instance, hsa_circ_022382 which is derived from the human FADS2 gene is overexpressed in 200 CRC tissues, where CircFADS2 overexpression was positively associated with clinicopathological features. In another study, hsa_circ_0026344 was shown to be significantly downregulated in 32 CRC patients compared to paired adjacent non-tumorous tissues. circRNAs in predicting response to chemoradiotherapy; hsa_circRNA_0001313 is one of the upregulated circRNAs in radio-resistant CRC tissues. Inhibition of hsa_circRNA_0001313 induces radio-sensitivity, reduced cell viability, and increases caspase-3 activity and colony formation by negatively modifying miR-338-3p in CRC cells. Another recent study reported that CircDDX17 was down-regulated in CRC, and its overexpression induced inhibition of 5-Fu resistance, blocked tumor growth, and CRC progression via sponging miR-31-5p . Interestingly, Circ-32883 was upregulated in CRC tissues and its overexpression was positively associated with chemoresistance through its potential action as a sponge for miR-501-5p. This miRNA binds to EML5 mRNA, inhibiting its expression. Thus, promoting resistance to FOLFOX therapy.
  • Results: CircFADS2 expression may therefore be a promising biomarker for prognostic investigation in CRC patients . The expression of hsa_ circ_0026344 was correlated with tumor size and lymph metastasis. Functionally, circRNA-0026344 overexpression significantly suppressed CRC cell proliferation and colony formation as well as promoted apoptosis by regulating miR-21 and miR-31 levels . Targeted therapy, chemotherapy, and multiagent regimens, for example, FOLFIRI (5-FU and irinotecan) and FOLFOX (5-FU oxaliplatin) can be applied as the standard treatment of CRC. Recent studies have shown that different ncRNAs such as circRNAs, may play important roles in the regulation of chemoresistance and affect the sensitivity of tumors to chemotherapy and radiotherapy through modification of various signaling pathways, including cell cycle, proliferation, apoptosis, and DNA damage repair .
  • Conclusion: circRNAs are an ideal biomarker in cancer, and are stably expressed in exosomes, blood, and saliva, where specific circRNAs have been indicated as promising prognostic or diagnostic biomarkers already. Abnormal expression of circRNAs has been observed in a wide range of human malignancies and their dysregulation can alter gene expression networks, leading to dramatic changes in cell fates, including cancer initiation and progression. circRNAs can be both oncogenicand anti-oncogenic, so could potentially be utilized in the treatment and prognosis of colorectal cancer. Although recent advances on circRNAs have highlighted some interesting insights, much work remains to be done to translate circRNAs into clinical application for clinical patient benefit.circRNAs have significant potential for the treatment and diagnosis of CRC.
  • Keywords: circRNAs ,Colorectal cancer , biomarkers , oncogenic