Shuai Zhang, Siguang Xu, Dandan Li, Songxin Wu, Miaomiao Han, Yifei Han, Zixi Wang, Dan Qiao, Hang Yuan, Baoshun Du, Hongwei Chen, Zheying Zhang
{"title":"The small protein LINC01547-ORF inhibits colorectal cancer progression by regulating the CLDN18-FAK-AKT axis.","authors":"Shuai Zhang, Siguang Xu, Dandan Li, Songxin Wu, Miaomiao Han, Yifei Han, Zixi Wang, Dan Qiao, Hang Yuan, Baoshun Du, Hongwei Chen, Zheying Zhang","doi":"10.62347/PNKH7683","DOIUrl":null,"url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA)-encoded small proteins play a major role in colorectal cancer. To identify more functional encoded small proteins, ribosome profiling data from colorectal cancer (CRC) cells were screened for ribosome-associated lncRNAs. The search identified LINC01547 that was shown to encode a small protein of 76 amino acids, termed LINC01547-ORF. Real-time quantitative fluorescence showed that LINC01547 expression was downregulated in colorectal cancer tissues. However, cell functional assays revealed that LINC01547 inhibited the proliferation and migration of colorectal cancer cell lines. Meanwhile, western blot and immunofluorescence assays confirmed that LINC01547 encoded LINC01547-ORF. Cellular functional assays indicated that compared with LINC01547 itself, LINC01547-ORF inhibited the proliferation and migration of colorectal cancer cell lines. Gene set enrichment analysis identified enrichment in the focal adhesion pathway and association with CLDN18 protein, whereas protein molecular docking models revealed interacting domains and amino acid residue sites. Of note, co-immunoprecipitation and immunofluorescence experiments showed that LINC01547-ORF could bind to the CLDN18 protein and that this interaction reduced CLDN18 ubiquitination, thereby promoting protein expression. Finally, western blot and immunofluorescence assays confirmed that LINC01547-ORF could target CLDN18 to inhibit the FAK/PI3K/AKT signaling pathway, suppressing colorectal cancer cell development. These findings suggest that the LINC01547-ORF-encoded small protein inhibits proliferation and migration in colorectal cancer, thereby offering a promising direction for treating this disease.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5504-5520"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626262/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/PNKH7683","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Long non-coding RNA (lncRNA)-encoded small proteins play a major role in colorectal cancer. To identify more functional encoded small proteins, ribosome profiling data from colorectal cancer (CRC) cells were screened for ribosome-associated lncRNAs. The search identified LINC01547 that was shown to encode a small protein of 76 amino acids, termed LINC01547-ORF. Real-time quantitative fluorescence showed that LINC01547 expression was downregulated in colorectal cancer tissues. However, cell functional assays revealed that LINC01547 inhibited the proliferation and migration of colorectal cancer cell lines. Meanwhile, western blot and immunofluorescence assays confirmed that LINC01547 encoded LINC01547-ORF. Cellular functional assays indicated that compared with LINC01547 itself, LINC01547-ORF inhibited the proliferation and migration of colorectal cancer cell lines. Gene set enrichment analysis identified enrichment in the focal adhesion pathway and association with CLDN18 protein, whereas protein molecular docking models revealed interacting domains and amino acid residue sites. Of note, co-immunoprecipitation and immunofluorescence experiments showed that LINC01547-ORF could bind to the CLDN18 protein and that this interaction reduced CLDN18 ubiquitination, thereby promoting protein expression. Finally, western blot and immunofluorescence assays confirmed that LINC01547-ORF could target CLDN18 to inhibit the FAK/PI3K/AKT signaling pathway, suppressing colorectal cancer cell development. These findings suggest that the LINC01547-ORF-encoded small protein inhibits proliferation and migration in colorectal cancer, thereby offering a promising direction for treating this disease.
期刊介绍:
The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.