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      Integrated analysis of TCGA data identifies endoplasmic reticulum stress-related lncRNA signature in stomach adenocarcinoma

      Author(s): 1 , 2 , 3 , 1 , 2
      Publication date Created:
      Publication date (Electronic):
      Journal: Oncologie
      Publisher: Walter de Gruyter GmbH

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          Abstract

          Objectives

          To investigaed the role of endoplasmic reticulum stress (ERS)-related long non-coding RNAs (lncRNAs) in stomach adenocarcinoma (STAD) using TCGA data.

          Methods

          This study integrated clinical, transcriptomic, and tumor data from the Cancer Genome Atlas (TCGA). The expression of ERS genes was evaluated, alongside their association with identified lncRNAs. Gene set enrichment analysis and immune cell infiltration analysis were performed to elucidate the biological pathways influenced by these lncRNAs.

          Results

          The study identified five lncRNAs – AC012055.1, LINC01235, LINC00571, LINC02073, and CFAP61-AS1 – strongly correlated with ERS pathways and cancer prognosis. A prognostic model based on these lncRNAs was developed and validated across low- and high-risk groups. Potential biological pathways associated with these lncRNAs were uncovered through immune cell infiltration and GSEA. Additionally, screening identified drugs potentially effective against STAD, highlighting co-expressed genes as probable therapeutic targets.

          Conclusions

          This research offers detailed insights into the molecular mechanisms of STAD, enhancing understanding of potential therapeutic targets and showing promise for clinical applications.

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          Most cited references45

          • Record: found
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          Mechanisms of long noncoding RNA function in development and disease

          Sandra Schmitz, Phillip Grote, Bernhard Herrmann (2016)
          Since decades it has been known that non-protein-coding RNAs have important cellular functions. Deep sequencing recently facilitated the discovery of thousands of novel transcripts, now classified as long noncoding RNAs (lncRNAs), in many vertebrate and invertebrate species. LncRNAs are involved in a wide range of cellular mechanisms, from almost all aspects of gene expression to protein translation and stability. Recent findings implicate lncRNAs as key players of cellular differentiation, cell lineage choice, organogenesis and tissue homeostasis. Moreover, lncRNAs are involved in pathological conditions such as cancer and cardiovascular disease, and therefore provide novel biomarkers and pharmaceutical targets. Here we discuss examples illustrating the versatility of lncRNAs in gene control, development and differentiation, as well as in human disease.
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            6-phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumor growth by inhibiting LKB1-AMPK signaling

            Ruiting Lin, Shannon Elf, Changliang Shan … (2015)
            The oxidative pentose phosphate pathway (PPP) contributes to tumor growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumor growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signaling. Moreover, we identified and developed 6PGD inhibitors, Physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumor growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.
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              Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer.

              MS Arredouani, B Lu, M Bhasin … (2009)
              Identification of novel biomarkers and immunotherapy targets for prostate cancer (PCa) is crucial to better diagnosis and therapy. We sought to identify novel PCa tumor-associated antigens (TAA) that are expressed in PCa, absent in nonprostate human tissue, and immunogenic for immune responses restricted by human HLA. Using microarray analysis of normal and cancerous human prostate tissues, we identified 1,063 genes overexpressed in PCa. After validating 195 transcripts in publicly available array data sets, we interrogated expression of these TAAs in normal human tissues to identify genes that are not expressed at detectable levels in normal, nonprostate adult human tissue. We identified 23 PCa TAA candidates. Real-time PCR confirmed that 15 of these genes were overexpressed in PCa (P< 0.05 for each). The most frequently overexpressed gene, single-minded homologue 2 (SIM2), was selected for further evaluation as a potential target for immunotherapy. ELISA assay revealed that a fraction of PCa patients exhibited immune responsiveness to SIM2 as evidenced by the presence of autoantibodies to SIM2 in their sera. We next showed binding of putative HLA-A2.1-restricted SIM2 epitopes to human A2.1, and immunization of transgenic HLA-A2.1 mice showed induction of SIM2-specific CTL responses in vivo. Our findings that SIM2 is selectively expressed in PCa, that human HLA-A2.1-restricted SIM2 epitopes induce specific T cells in vivo, and that anti-SIM2 antibodies are detectable in PCa patients' sera implicate SIM2 as a PCa-associated antigen that is a suitable potential target for PCa immunotherapy.
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                Author and article information

                Journal
                Title: Oncologie
                Publisher: Walter de Gruyter GmbH
                ISSN (Electronic): 1765-2839
                Publication date Created: March 21 2024
                Publication date Created: November 21 2023
                Publication date Created: March 01 2024
                Publication date (Print): March 21 2024
                Publication date (Electronic): January 01 2024
                Publication date (Print): March 01 2024
                Volume: 26
                Issue: 2
                Pages: 221-237
                Affiliations
                [1 ]State Key Laboratory of Component-based Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin , China
                [2 ]Haihe Laboratory of Modern Chinese Medicine , Tianjin , China
                [3 ]Inner Mongolia Autonomous Region Institute of Ultrasound Imaging , Ordos Central Hospital , Ordos City , Inner Mongolia Autonomous Region , China
                Article
                DOI: 10.1515/oncologie-2023-0394
                SO-VID: a25784a4-294f-4665-a2eb-8035ea6fe086
                Copyright © © 2024
                License:

                http://creativecommons.org/licenses/by/4.0

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