Long non-coding RNAs have important roles in the occurrence and progression of various cancers. However, the molecular mechanism of lncRNAs in colorectal cancer (CRC) is not well illustrated. Thus, we used bioinformatics methods to find potential lncRNAs associated with CRC progression, and chose SH3PXD2A-AS1 as a candidate for further analysis. The roles of SH3PXD2A-AS1 in CRC cells were determined by CCK-8, transwell invasion, wound healing and flow cytometry assays. Besides, we established the CRC tumor models in nude mice to study the effect of SH3PXD2A-AS1 on the tumor growth. Based on the ceRNA hypothesis, we used miRDB and miRTarBase websites to identify the SH3PXD2A-AS1-related ceRNA regulatory network, and measured the roles of this network in CRC cells. The results revealed that the expression profiles of SH3PXD2A-AS1 from GEO and TCGA databases showed an aberrant high level in CRC tissues compared with colorectal normal tissues. SH3PXD2A-AS1 over-expression was also found in CRC cells. SH3PXD2A-AS1 knockdown inhibited the CRC cellular proliferation, invasion and migration but induced apoptosis. Besides, SH3PXD2A-AS1 knockdown also suppressed the growth of CRC tumors. Furthermore, SH3PXD2A-AS1 could function as a ceRNA of miR-330-5p. Additionally, UBA2 was proved to be a target gene of miR-330-5p. Moreover, SH3PXD2A-AS1 knockdown downregulated UBA2 expression through sponging miR-330-5p to inactivate the Wnt/β-catenin signaling pathway, thereby inhibiting the cell growth and promoting apoptosis. Therefore, the SH3PXD2A-AS1/miR-330-5p/UBA2 network could regulate the progression of CRC through the Wnt/β-catenin pathway. These findings offer new sights for understanding the pathogenesis of CRC and provide potential biomarkers for CRC treatment.

中文翻译：

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SH3PXD2A-AS1/miR-330-5p/UBA2 ceRNA网络通过调节Wnt/β-catenin信号通路的活性介导结直肠癌的进展

长链非编码 RNA 在各种癌症的发生和发展中具有重要作用。然而，lncRNAs 在结直肠癌 (CRC) 中的分子机制尚未得到很好的说明。因此，我们使用生物信息学方法寻找与 CRC 进展相关的潜在 lncRNA，并选择 SH3PXD2A-AS1 作为进一步分析的候选者。SH3PXD2A-AS1 在 CRC 细胞中的作用由 CCK-8、transwell 侵袭、伤口愈合和流式细胞术测定确定。此外，我们在裸鼠中建立CRC肿瘤模型以研究SH3PXD2A-AS1对肿瘤生长的影响。基于 ceRNA 假设，我们使用 miRDB 和 miRTarBase 网站来识别 SH3PXD2A-AS1 相关的 ceRNA 调控网络，并测量该网络在 CRC 细胞中的作用。结果表明，与结直肠正常组织相比，来自 GEO 和 TCGA 数据库的 SH3PXD2A-AS1 的表达谱在 CRC 组织中显示出异常的高水平。在 CRC 细胞中也发现 SH3PXD2A-AS1 过度表达。SH3PXD2A-AS1 敲低抑制 CRC 细胞增殖、侵袭和迁移，但诱导细胞凋亡。此外，SH3PXD2A-AS1 敲低也抑制了 CRC 肿瘤的生长。此外，SH3PXD2A-AS1 可以作为 miR-330-5p 的 ceRNA 发挥作用。此外，UBA2被证明是miR-330-5p的靶基因。此外，SH3PXD2A-AS1敲低通过海绵miR-330-5p使Wnt/β-catenin信号通路失活来下调UBA2表达，从而抑制细胞生长并促进细胞凋亡。所以，SH3PXD2A-AS1/miR-330-5p/UBA2网络可以通过Wnt/β-catenin通路调控CRC的进展。这些发现为了解 CRC 的发病机制提供了新的视角，并为 CRC 的治疗提供了潜在的生物标志物。