Long Non-coding RNA LINC02195 as a Regulator of MHC I Molecules and Favorable Prognostic Marker for Head and Neck Squamous Cell Carcinoma

Abstract

The loss of major histocompatibility complex class I (MHC I) molecules is an important mechanism by which cancer cells escape immunosurveillance in head and neck squamous cell carcinoma (HNSCC). Several long non-coding RNAs (lncRNAs) have been implicated in immune response and regulation including antigen processing and presentation. However, few studies on lncRNAs regulating MHC I expression in HNSCC have been conducted. In this study, MHC I related lncRNAs were identified from the The Cancer Genome Atlas (TCGA) HNSCC database. One of the lncRNAs, long intergenic non-protein coding RNA 2195 (LINC02195), was found to be associated with genes encoding MHC I molecules and patient prognosis in the TCGA database. KEGG and GO analyses suggested that LINC02195 was closely related to antigen processing and presentation. qRT-PCR revealed high expression of LINC02195 in human HNSCC tissues and HNSCC cell lines compared with normal mucosal tissues. in situ hybridization of the HNSCC tissue microarray revealed a correlation between high LINC02195 expression and a favorable prognosis in our patient cohort. Silencing of LINC02195 decreased MHC I protein expression, as evidenced by western blotting. Multiplex immunochemistry was performed to reveal the positive correlation between high LINC02195 expression and an increased number of CD8 + and CD4 + T cells in the tumor microenvironment. Based on our study, LINC02195 is a promising prognostic marker and a target for future therapeutic interventions.

Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation

“…ncRNAs can also be positive regulators of MHC I. For example, in head and neck squamous cell carcinomas, expression of the lncRNA, lnc02195, increases MHC I expression and is associated with a better prognosis ( 208 ). In nasopharyngeal carcinomas miR9 expression increases expression of MHC I molecules and TAP1 ( 209 ).…”

Identification of Immune-Related LncRNA Pairs for Predicting Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma

“…The loss of major histocompatibility complex I (MHC I) molecules is an important mechanism for HNSCC cells to evade immune surveillance. However, LINC02195 is a crucial regulator of MHC I molecules ( 45 ). Moreover, novel lncRNA SFTA1P promotes tumor growth by downregulating miR-4766-5p via the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma ( 46 ).…”

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

“…Li et al also found out that silencing LINC02195 expression causes a decrease in the level of MHC I molecules and definitely proved that patients with high expression of this lincRNA have a better prognosis. Further research indicated that this lincRNA is immune-related due to its significant correlation with the T cell receptor pathway, chemokines (class I and II), and cytokines [91]. The discovered association with lymphocytes T suggests better infiltration of tumor tissue, which leads to the positive response to immunotherapy and better prognosis, not only in HNSCC but in many different cancers [91][92][93].…”

“…Long non-protein-coding RNA 2195 (LINC02195) is closely associated with major histocompatibility complex class I (MHC I) molecules, whose lack of function leads to the mechanism of escaping immunosurveillance by tumor in HNSCC [91,92]. Analysis of LINC02195 expression patterns showed significantly higher lincRNA levels in HNSCC tumor samples than in cell lines derived from dysplastic tissue or normal mucosa.…”