Abstract
BackgroundLong noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC).MethodsDifferentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo.ResultsWe systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy.ConclusionMIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.
Highlights
Long noncoding RNAs are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers
We found that the expression of these common lincRNAs can effectively distinguish the cancer patients from the normal controls in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) (Fig. 1b)
The Venn plot in red color shows the up-regulated lincRNAs and the blue ones show the down-regulated lincRNAs in cancer. b, Heat maps show the expression of lincRNAs that are differentially expressed both in COAD and READ. c and d, The number of literature that co-occurred with cancer for each lincRNA. c is for up-regulated lincRNAs and d is for down-regulated lincRNAs. e, The boxplots show the distribution of MIR22 Host Gene (MIR22HG) expression in normal and cancer samples
Summary
Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. We are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC). With the development of next-generation sequencing technology, it is realized that the most part of human genome is transcribed to noncoding RNAs [2]. Of these newly discovered RNA regulatory elements, long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes [3,4,5]. The genome-wide expression pattern and function of lncRNAs in CRC still need to be analyzed
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