6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      LRPPRC facilitates tumor progression and immune evasion through upregulation of m 6A modification of PD-L1 mRNA in hepatocellular carcinoma

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          LRPPRC is a newly discovered N 6-methyladenosine (m 6A) modification reader, which potentially affects hepatocellular carcinoma (HCC) progression. PD-L1 in tumor cells is essential for tumor immune evasion. This work investigated the LRPPRC-mediated m 6A-modification effect on PD-L1 mRNA and immune escape in HCC.

          Methods

          Expression and clinical implication of LRPPRC and PD-L1 were measured in human HCC cohorts. The influence of LRPPRC on malignant behaviors of HCC cells was investigated through in vitro assays and xenograft tumor murine models. The posttranscriptional mechanism of LRPPRC on PD-L1 and anti-tumor immunity was elucidated in HCC cells via RIP, MeRIP−qPCR, RNA stability, immunohistochemical staining, and so forth.

          Results

          LRPPRC exhibited the notable upregulated in human HCC tissues, which was in relation to advanced stage and worse overall survival and disease-free survival. Impaired proliferative capacity and G2/M phage arrest were found in LRPPRC-knockout cells, with increased apoptotic level, and attenuated migratory and invasive abilities. In HCC patients and murine models, LRPPRC presented a positive interaction with PD-L1, with negative associations with CD8+, and CD4+ T-cell infiltrations and chemokines CXCL9, and CXCL10. LRPPRC loss downregulated the expression of PD-L1 and its m 6A level in HCC cells. Moreover, LRPPRC suppression mitigated tumor growth in murine models and improved anti-tumor immunity and immune infiltration in tumors.

          Conclusion

          This work unveiled that LRPPRC may posttranscriptionally upregulate PD-L1 partially with an m 6A-dependent manner for heightening mRNA stabilization of PD-L1 and provided a new mechanism for m 6A regulator-mediated immunosuppression in HCC.

          Related collections

          Most cited references34

          • Record: found
          • Abstract: found
          • Article: not found

          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            TIMER2.0 for analysis of tumor-infiltrating immune cells

            Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor–immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis

              Abstract Introduced in 2017, the GEPIA (Gene Expression Profiling Interactive Analysis) web server has been a valuable and highly cited resource for gene expression analysis based on tumor and normal samples from the TCGA and the GTEx databases. Here, we present GEPIA2, an updated and enhanced version to provide insights with higher resolution and more functionalities. Featuring 198 619 isoforms and 84 cancer subtypes, GEPIA2 has extended gene expression quantification from the gene level to the transcript level, and supports analysis of a specific cancer subtype, and comparison between subtypes. In addition, GEPIA2 has adopted new analysis techniques of gene signature quantification inspired by single-cell sequencing studies, and provides customized analysis where users can upload their own RNA-seq data and compare them with TCGA and GTEx samples. We also offer an API for batch process and easy retrieval of the analysis results. The updated web server is publicly accessible at http://gepia2.cancer-pku.cn/.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 March 2023
                2023
                : 14
                : 1144774
                Affiliations
                [1] 1 Department of General Surgery, The Affiliated Bozhou Hospital of Anhui Medical University , Bozhou, Anhui, China
                [2] 2 Department of Gastroenterology, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China
                [3] 3 Department of Cancer Radiotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Cancer Hospital) , Hefei, Anhui, China
                [4] 4 Faculty of Health and Life Sciences, Oxford Brookes University , Oxford, United Kingdom
                [5] 5 Department of Comprehensive Surgery, Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC , Hefei, Anhui, China
                Author notes

                Edited by: Jian Song, University Hospital Münster, Germany

                Reviewed by: Lijie Chen, China Medical University, China; Anm Nazmul Khan, University at Buffalo, United States

                *Correspondence: Heng Li, jxna36@ 123456163.com

                †These authors have contributed equally to this work

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2023.1144774
                10097877
                37063837
                0014d33e-b9ba-4eb0-8bb5-71c683a6b2fa
                Copyright © 2023 Wang, Tang, Cui, Gong and Li

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2023
                : 07 March 2023
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 34, Pages: 15, Words: 4513
                Funding
                This work was funded by Project of Bozhou Municipal Health Commission (bzwj2022a001), Project of Bozhou Science and Technology Bureau (bzzc2022008), Project of The Affiliated Bozhou Hospital of Anhui Medical University (by2022001, by2023001).
                Categories
                Immunology
                Original Research

                Immunology
                hepatocellular carcinoma,lrpprc,pd-l1,immune evasion,m6a modification,anti-tumor immunity,tumor progression

                Comments

                Comment on this article