Abstract
BackgroundColorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health. An increasing number of studies have reported that circular RNA (circRNA) is involved in the progression of CRC. In this study, the special profiles of circASXL1 (circ_0001136) in CRC progression were revealed.MethodsThe expression of circASXL1, microRNA-1205 (miR-1205), and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression was determined by Western blot or immunohistochemistry. Cell colony-forming ability was investigated by colony formation assay. Cell cycle and apoptosis were demonstrated using cell-cycle and cell-apoptosis analysis assays, respectively. Cell migration and invasion were detected by wound-healing and transwell migration and invasion assays, respectively. The binding sites between miR-1205 and circASXL1 or GRIK3 were predicted by circBank or miRDB online database, and identified by dual-luciferase reporter assay. The impact of circASXL1 on tumor formation in vivo was investigated by in vivo tumor formation assay.ResultsCircASXL1 and GRIK3 expression were apparently upregulated, and miR-1205 expression was downregulated in CRC tissues and cells relative to control groups. CircASXL1 knockdown inhibited cell colony-forming ability, migration and invasion, whereas induced cell arrest at G0/G1 phase and cell apoptosis in CRC cells; however, these effects were attenuated by miR-1205 inhibitor. Additionally, circASXL1 acted as a sponge for miR-1205, and miR-1205 was associated with GRIK3. Furthermore, circASXL1 silencing hindered tumor formation by upregulating miR-1205 and downregulating GRIK3 expression.ConclusionCircASXL1 acted an oncogenic role in CRC malignant progression via inducing GRIK3 through sponging miR-1205. Our findings provide a theoretical basis for studying circASXL1-directed therapy for CRC.
Highlights
Colorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health
CircASXL1 expression was obviously upregulated in CRC tissues and cells To figure out the expression pattern of circASXL1, located in chr20:30954186-30956926 and formed from exons 2 and 3 of ASXL transcriptional regulator 1 (ASXL1) (Fig. S1), in CRC tissues, we firstly predicted circASXL1 expression through GEO dataset (GSE142837)
CircASXL1 functioned as an oncogene in CRC malignant progression by regulating cell proliferation, motility, and apoptosis
Summary
Colorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health. Circ_004680 facilitated CRC cell proliferation and migration [11]; circ_0007142 silencing hindered cell proliferation and tumor metastasis by sponging microRNA-1225p (miR-122-5p) in CRC [12]. In another example, Tian et al explained that circ_0025033 accelerated CRC cell proliferation and invasion, whereas inhibited cell apoptosis via binding to miR-143-3p [13]. ASXL transcriptional regulator 1 (ASXL1), a cancer-associated gene, has been reported to hinder cell growth in CRC [14]; whether circASXL1, a circRNA formed from ASXL1 gene, participates in CRC progression remains unknown. This study was designed to reveal the role of circASXL1 in CRC progression
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