br Conflict of interest br Introduction Colorectal cancer
Conflict of interest
Introduction Colorectal cancer (CRC), characterized by high prevalence in elderly people, is one of the most common cancers of digestive tract. CRC severely affects human health and causes enormous social and economic burdens [, , ]. Although public health awareness efforts and preventive measures have achieved tremendous progress in recent decades, the incidence of CRC remains high worldwide, especially in Europe and North America . In 2016, CRC accounted for more than 90,000 new cases and had an almost 50% fatality rate in the United State [3,4]. The prognosis of CRC patients has been improving during the past few years. Data have shown that the 5-year survival rate of CRC patients with regional spread is almost 70%; however, due to distant tumor metastasis, the 5-year survival rate of patients with advanced stages of CRC is only 12% . Therefore, exploring the pathogenesis mechanisms of CRC is urgent and essential for treating CRC patients. It is well known that non-coding RNAs consist of various different RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and small interfering RNAs (siRNAs) [6,7]. Circular RNAs (circRNAs), which are produced primarily through back-splicing, are a novel subtype of non-coding RNAs that formed a closed loop without 5′-3′ ends and poly A tail [8,9]. Previous studies have indicated that circRNAs may participate in the regulation of gene why not by acting as miRNAs sponges, suggesting that the circRNAs/miRNA/mRNA axis may play an important role in the gene expression associated with diseases, including cancers [10,11]. Although the exact functions of circRNAs remain unclear, accumulating evidence has demonstrated that circRNAs are involved in the progression and development of various tumors, such as gastric cancer, breast cancer, and lung cancer [10,12,13].
Materials and methods
Discussion Tremendous progress has been achieved in understanding the pathogenic mechanisms of CRC during the past decades; however, effective therapeutic measures remain limited [14,15]. Currently, the most effective treatments for CRC continue to be mainly confined to surgical removal and neoadjuvant therapy, which provide limited effects and poor prognosis, especially in patients with distant metastasis . Therefore, it is urgent to identify new and effective molecular targets for the prevention, diagnosis, and treatment of CRC. Previous studies have suggested that miRNAs and lncRNAs might be molecular markers and potential therapeutic targets by acting as gene regulators for the diagnosis and treatment of various cancers. Recently, circRNAs were also reported to be involved in the progression of many tumors, such as gastric cancer, lung cancer, and breast cancer; however, few studies have demonstrated that circRNAs are involved in CRC [12,13,16]. hsa_circ_0071589 is a novel circular RNA that has been found to be upregulated in CRC tissues relative to corresponding normal tissues, suggesting that it may play a role in the progression and development of CRC. The functional experiments showed that hsa_circ_0071589 knockdown in HCT116 cells inhibited cell proliferation, invasion, and migration, implying that it may act as an oncogene in CRC. Accumulating evidence has suggested that the circRNAs/miRNAs/mRNAs axis is involved in the pathogenesis of many tumors, including bladder cancer, osteosarcoma, and breast cancer [11,17,18]. Therefore, we wonder whether hsa_circ_0071589 exerts its oncogenic effects by miRNA. Studies have demonstrated that a large number of miRNAs are related to the pathogenesis of CRC, such as miR-495, miR-411, miR-215-5p, and miR-600 [, , , ]. Among them, miR-600 was reported to function as tumor suppressor in human colorectal cancer by targeting p53 . Thus, it was chosen for further research. In our research, the bioinformatics analysis predicted that there was a binding site for miR-600 in hsa_circ_0071589, which was validated by the subsequent luciferase reporter assay. The results also showed that miR-600 expression could be regulated by hsa_circ_0071589 in the CRC cell line and revealed a negative correlation between hsa_circ_0071589 and miR-600.