LINC00460/miR-186-3p/MYC feedback loop facilitates colorectal cancer immune escape by enhancing CD47 and PD-L1 expressions.

Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE

Publication: 2009- : London : BioMed Central
Original Publication: [Roma] : APSIT,

Colorectal Neoplasms*/genetics ; Colorectal Neoplasms*/pathology ; Colorectal Neoplasms*/metabolism ; Colorectal Neoplasms*/immunology ; MicroRNAs*/genetics ; CD47 Antigen*/metabolism ; CD47 Antigen*/genetics ; RNA, Long Noncoding*/genetics ; RNA, Long Noncoding*/metabolism ; B7-H1 Antigen*/metabolism ; B7-H1 Antigen*/genetics; Humans ; Mice ; Animals ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Tumor Escape/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Male ; Female ; Cell Proliferation ; Feedback, Physiological ; Prognosis ; Mice, Nude

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.
(© 2024. The Author(s).)

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82173236 National Natural Science Foundation of China

Keywords: CD47; Colorectal cancer; LINC00460; MYC; PD-L1; miR-186-3p

0 (MicroRNAs)
0 (CD47 Antigen)
0 (RNA, Long Noncoding)
0 (B7-H1 Antigen)
0 (CD274 protein, human)
0 (CD47 protein, human)
0 (Proto-Oncogene Proteins c-myc)
0 (MYC protein, human)

Date Created: 20240812 Date Completed: 20240813 Latest Revision: 20240923

20240923

PMC11321182

10.1186/s13046-024-03145-1

39135122