journal contribution
posted on 2023-03-31, 02:21 authored by Jie Xu, Qingtao Meng, Xiaobo Li, Hongbao Yang, Jin Xu, Na Gao, Hao Sun, Shenshen Wu, Giuseppe Familiari, Michela Relucenti, Haitao Zhu, Jiong Wu, Rui Chen This file contains supplemental materials and methods, supplemental tables: ST1 Demographic characteristics of CRC patients recruited for microarray assay, ST2: Distributions of demographic and clinicopathologic characteristics of patients recruited for TMA; ST3: Demographic information of colorectal adenoma (ADE) patients for PCR analysis; ST4:Demographic information of colorectal cancer (CRC) patients for PCR analysis; supplemental figures SF1:Construction of an immunity-associated network involved in CRC progression; SF2:Roles of RELA and MIR17HG in murine AOM-DSS models and CRC cohorts; SF3:miR-17-5p promotes CRC tumorigenesis; SF4: MIR17HG promotes CRC tumorigenesis through suppressing BLNK; SF5: MIR17HG promotes CRC tumorigenesis through binding to miR-17-3p in vitro and in vivo; SF6: Regulation of MALT1, NFKBIE, PPP3R1 and MAP3K7 by miR-17-3p in CRC; SF7: Expression levels of PD-L1 mRNA in cells; SF8: Expression levels of PD-L1 protein in tumor tissues
Funding
National Natural Science Foundation of China
Ministry of Foreign Affairs and International Cooperation of Italy
Natural Science Foundation of Jiangsu Province
Six Talent Peaks Project in Jiangsu Province
Postgraduate Research and Practice Innovation Program of Jiangsu
History
ARTICLE ABSTRACT
Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both in vitro and in vivo. Mechanistically, MIR17HG increased the expression of NF-κB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target.
These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.
