Background: This study tried to explore the mechanism of long non-coding RNA (lncRNA) KCNQ1OT1 in tumor immune escape.Methods: Gene Expression Omnibus (GEO) and microarray analysis were used to screen the differentially expressed lncRNA and microRNA (miRNA) in normal tissues and tumor tissues. Quantitative reverse transcription PCR (RT-qPCR) was used to quantify KCNQ1OT1, miR-30a-5p, ubiquitin-specific peptidase 22 (USP22), and programmed death-ligand 1 (PD-L1). The interactive relationship between KCNQ1OT1 and miR-30a-5p was verified using dual-luciferase reporter gene assay and ribonucleoprotein immunoprecipitation (RIP) assay. Cell Counting Kit (CCK)-8, clone formation, wound healing, and apoptosis are used to detect the occurrence of tumor cells after different treatments. Protein half-life and ubiquitination detection are used to study the influence of USP22 on PD-L1 ubiquitination. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo.Results: The expression of lncRNA KCNQ1OT1 in tumor tissues and tumor cell-derived exosomes was significantly increased. The tumor-promoting effect of lncRNA KCNQ1OT1 was through the autocrine effect of tumor cell-derived exosomes, which mediates the miR-30a-5p/USP22 pathway to regulate the ubiquitination of PD-L1 and inhibits CD8+ T-cell response, thereby promoting colorectal cancer development.Conclusion: Tumor cell-derived exosomes’ KCNQ1OT1 could regulate PD-L1 ubiquitination through miR-30a-5p/USP22 to promote colorectal cancer immune escape.

We aimed to explore the mechanism of the KCNQ 1 OT 1/miR‐760/ PPP 1R1B axis acting to regulate methotrexate ( MTX ) resistance of colorectal cancer ( CRC ). Differentially expressed mRNA s and lnc RNA s in MTX ‐sensitive CRC cell lines and MTX ‐resistant cell lines were determined through microarray analysis. Application of bioinformatics analysis was aimed to uncover the relationships among the lnc RNA s/mi RNA s/ mRNA s, and to demonstrate the effects of cAMP signalling pathway in MTX ‐resistant CRC . The expression level of RNA and proteins was, respectively, detected using qRT ‐ PCR and Western blot assays, whereas the dual‐luciferase reporter gene assay was implemented to verify the targeted relationship. The influence of the lnc RNA /mi RNA / mRNA axis on biological functions of MTX ‐resistant cells and on the growth of tumours determined through both vitro and vivo experiments. Lnc RNA KCNQ 1 OT 1 and PPP 1R1B mRNA were overexpressed in MTX ‐resistant CRC tumour cells. KCNQ 1 OT 1 functioned as a sponge of miR‐760, which targeted PPP 1R1B . Knockdown of KCNQ 1 OT 1 enhanced chemosensitivity towards MTX through the sponging of miR‐760. MiR‐760 expressed at low levels targeted PPP 1R1B in the activated cAMP signalling pathway under MTX treatment. Knockdown of KCNQ 1 OT 1 dampened the proliferation of MTX ‐resistant ( HT 29/ MTX ) cells by regulating the miR‐760/ PPP 1R1B axis, which also induced cell cycle arrest together with apoptosis. KCNQ 1 OT 1 regulated the expression of PPP 1R1B and the downstream genes CREB and CBP in the cAMP signalling pathway. MTX showed a suppressive function on CRC progression. KCNQ 1 OT 1 enhanced the MTX resistance of ...

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