Hsa_circ_0087862 contributes to the progression of colorectal cancer through regulating miR-512-3p/HK2 axis

Colorectal cancer (CRC) occupies a place in malignant tumors, with the third highest incidence in the world [1], [2], [3]. Although screening, diagnostic and therapeutic tools have greatly improved 5-year survival in CRC patients, unfortunately, there are very few initiatives to effectively treat CRC due to two major reasons: late diagnosis and susceptibility to recurrence [4]. Therefore, there is a need to understand the molecular mechanisms underlying the pathogenesis of CRC and to identify accurate and efficient biomarkers.

Extensive evidence suggested that circular RNAs (circRNAs), as a class of non-coding RNA molecules, have been implicated as players in various diseases. Up-regulated circ_0000039 expression in gastric cancer was effectively correlated with poor differentiation of tumor tissues [5]. Low of circ-0050102 expression contributed to cell apoptosis and arrested cell cycle in pancreatic cancer [6]. Circ-VPS18 silencing blocked glioma development via miR-370/RUNX1 axis [7]. Circ_0001982 facilitated CRC development by sponging miR-144 [8]. Hsa_circ_0087862 was highly expressed in lung cancer [9]. Moreover, Xiao et al. reported that circ_0087862 knockdown restrained CRC cell proliferation, invasion and glycolysis and facilitated CRC cell apoptosis [10]. The available information against circRNAs in CRC treatment was limited, therefore, this study investigated circ_0087862 in depth.

MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules containing about 22 nucleotides [11]. Multiple lines of evidence suggested that miRNAs were involved in the physiology of a wide range of diseases. For example, miR-1246 promoted CRC cell migration [12], miR-17 acted as an oncogene in CRC [13]. To our knowledge, miR-512–3p was under-expressed in retinoblastoma, and it curbed cell proliferation [14]. However, no study reported miR-512–3p was correlated with circ_0087862-mediated network in CRC. Hence, we attempt to explore the relation between circ_0087862 and miR-512–3p in CRC progress.

Hexokinase 2 (HK2), belonging to HK family, is a critical mediator of aerobic glycolysis [15]. HK2 was highly expressed in CRC cells [16]. However, the regulation mechanism of HK2 on CRC needs to be known as soon as possible.

Many studies have demonstrated that circRNAs affect the progression of diverse biological behaviors in human disease by targeting miRNAs, which then alter gene expression [17], [18], [19]. Thus, in this study we explored the relations of circ_0087862, miR-512–3p and HK2 in CRC progression, expecting to obtain a novel regulatory network in CRC progression. In general, our findings investigate circ_0087862 function on cell proliferation and apoptosis in CRC, and highlight the circ_0087862/miR-512–3p/HK2 network.

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