LncRNA AF117829.1 is correlated with prognosis and immune infiltration and facilitates tumor progression by targeting OR7C1 in colorectal cancer.

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system with a high incidence, a poor prognosis and an unsatisfactory therapeutic effect. Long non-coding RNAs (lncRNAs) play crucial roles in various biological processes related to tumor progression. Immune-related lncRNA gene AF117829.1 has been reported to participate in the construction of clinical predictive signature in CRC patients, suggesting that it may be involved in regulating the immune landscape and progression of CRC. However, the clinical and immunological significance and biological function of AF117829.1 in CRC remain unclear. In this study, we aim to explore the roles of AF117829.1 in CRC progression by bioinformatics analysis and experimental studies, thereby providing new targets for CRC treatment.

Methods: This study collected data from The Cancer Genome Atlas (TCGA) database and explored the role of AF117829.1 in CRC by bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods estimated the immune infiltration. Gene Set Enrichment Analysis (GSEA) was performed to evaluate the enrichment of functional pathways and gene signatures. The biological functions and mechanism of AF117829.1 in CRC progression were validated using CRC tissues and in vitro experiments.

Results: In our study, high expression of AF117829.1 was found in pan-cancer including CRC and was positively associated with tumor (T) stage and tumor-node-metastasis (TNM) stage in CRC. The survival analysis results showed that CRC patients with high-AF117829.1 expression had significantly shorter overall survival (OS) time than those with low-AF117829.1 expression. Moreover, AF117829.1 expression was negatively associated with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Subsequently, AF117829.1 expression was confirmed to be significantly associated with StromalScore, immune cell infiltration (ICI) levels and immune checkpoints (ICP) genes expression in CRC. The immunophenoscore (IPS) results indicated that immunotherapy could be more effective in CRC patients with low-AF117829.1 expression. Then we confirmed that AF117829.1 was highly expressed in CRC cell lines and tissues. Furthermore, our GSEA results showed that olfactory transduction-related signaling pathways were significantly enriched in the high-AF117829.1 expression group. Finally, in vitro experiments confirmed that AF117829.1 overexpression promoted the proliferation, migration and invasion of CRC cells by targeting olfactory receptor family 7 subfamily C member 1 (OR7C1).

Conclusions: LncRNA AF117829.1 is closely related to the prognosis, immunological characteristics and immunotherapy response of CRC patients and promotes malignant progression of CRC by targeting OR7C1. Moreover, AF117829.1 may be a potential therapeutic target for CRC patients.