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Abstract：
BACKGROUND: Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated.
METHODS: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. RESULTS: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop.
CONCLUSIONS: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.
METHODS: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. RESULTS: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop.
CONCLUSIONS: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.
摘要：
背景：长链非编码RNA（LncRNA）被认为是癌症肿瘤发生和发展的关键调节因子。然而,它们在结直肠癌(CRC)中的功能和分子机制仍有待进一步阐明.
方法：LINC00460通过人CRC和正常组织之间的差异分析进行鉴定，并通过原位杂交（ISH）和qRT-PCR进行验证。我们通过体外和体内实验研究了LINC00460在CRC中的生物学功能。我们通过生物信息学分析预测了LINC00460的作用机制和下游功能分子,并通过双荧光素酶报告基因测定证实了它们，RNA免疫沉淀(RIP),RNA下拉，等。结果：发现LINC00460在CRC中显著过表达，并与不良预后相关。过表达LINC00460促进CRC细胞免疫逃逸，重塑抑制性肿瘤免疫微环境，从而促进CRC增殖和转移。机制研究表明，LINC00460作为miR-186-3p的分子海绵，然后提升了MYC的表达式，CD47和PD-L1促进CRC细胞免疫逃逸。我们还证明MYC在转录水平上调LINC00460表达并形成正反馈环。
结论：LINC00460/miR-186-3p/MYC反馈环促进CRC细胞免疫逃逸，进而促进CRC增殖和转移。我们的发现为LINC00460作为CRC免疫调节剂提供了新的见解，并为CRC患者提供潜在的治疗靶点。
方法：LINC00460通过人CRC和正常组织之间的差异分析进行鉴定，并通过原位杂交（ISH）和qRT-PCR进行验证。我们通过体外和体内实验研究了LINC00460在CRC中的生物学功能。我们通过生物信息学分析预测了LINC00460的作用机制和下游功能分子,并通过双荧光素酶报告基因测定证实了它们，RNA免疫沉淀(RIP),RNA下拉，等。结果：发现LINC00460在CRC中显著过表达，并与不良预后相关。过表达LINC00460促进CRC细胞免疫逃逸，重塑抑制性肿瘤免疫微环境，从而促进CRC增殖和转移。机制研究表明，LINC00460作为miR-186-3p的分子海绵，然后提升了MYC的表达式，CD47和PD-L1促进CRC细胞免疫逃逸。我们还证明MYC在转录水平上调LINC00460表达并形成正反馈环。
结论：LINC00460/miR-186-3p/MYC反馈环促进CRC细胞免疫逃逸，进而促进CRC增殖和转移。我们的发现为LINC00460作为CRC免疫调节剂提供了新的见解，并为CRC患者提供潜在的治疗靶点。
