{
  "abstract": "The conserved non-coding RNA 7SK is a well-established global transcriptional repressor, yet its context-specific functions in cancer and therapy resistance remain paradoxical. Here, we resolve this paradox by uncovering a dual-axis mechanism through which 7SK drives colorectal cancer (CRC) resistance. By integrating single-cell multi-omics with functional assays, we demonstrate that 7SK not only selectively activates the JUN transcriptional network to fuel tumor proliferation but also reduces global transcriptional entropy to stabilize an immunosuppressive microenvironment and promote immune escape. This “local activation-global suppression” paradigm is conserved across multiple cancer types, positioning 7SK as a potential pan-cancer therapeutic target. Our findings reveal 7SK as a dynamic modulator that balances oncogene-specific transcription with global transcriptional suppression across cancers, providing a new framework for understanding and targeting ncRNA-mediated resistance. Author summary: Why does a molecule known for shutting down gene activity actually help tumors survive chemotherapy? This intriguing paradox motivated our investigation. Using single-cell technologies to analyze patient tumor samples, we found that in chemotherapy-resistant colorectal cancer cells, the non-coding RNA 7SK selectively amps up a specific set of proliferation-driving genes through the JUN network, pressing the accelerator on tumor growth. At the same time, it broadly dampens overall gene expression disorder, which quiets immune alarm signals and creates a “cold” tumor environment that evades immune attack. This dual strategy of local activation paired with global suppression helps resistant clones thrive under therapeutic pressure. Remarkably, we observed the same mechanism operating across multiple cancer types, suggesting that 7SK’s role is not a cancer-specific quirk but a conserved survival program. Our findings reframe 7SK from a simple repressor to a master conductor of transcriptional balance in cancer. By uncovering 7SK’s dual role, we lay a foundation for future therapeutic strategies aimed at disrupting this mechanism to overcome drug resistance.",
  "abstract_shown": true,
  "affiliations": [
    "BGI Research, Chongqing, China",
    "BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China",
    "College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China",
    "State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China",
    "BGI Research, Kunming, China",
    "Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China",
    "Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China",
    "Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China",
    "Department of Obstetrics and Reproductive Medicine, Affiliated Hospital of Yunnan University, Kunming, Yunnan, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ping Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zile Luo"
    },
    {
      "affs": [
        2
      ],
      "name": "Xi Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhongyang Yuan"
    },
    {
      "affs": [
        4
      ],
      "name": "Le Cheng"
    },
    {
      "affs": [
        5
      ],
      "name": "Yi Yang"
    },
    {
      "affs": [
        6
      ],
      "name": "Hongcheng Lin"
    },
    {
      "affs": [
        7
      ],
      "name": "Qiong Zhang"
    },
    {
      "affs": [
        8
      ],
      "name": "Pengfei Qin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/503z46m8zwh6n.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pcbi.1014749",
  "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014749",
  "id": "503z46m8zwh6n",
  "issns": [
    "1553-7358"
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  "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014749",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer-related molecular mechanisms research"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/DNA transcription"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcriptional control"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Transcriptome analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Cloning"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer treatment"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Colorectal cancer"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Thermodynamics/Entropy"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Cloning"
    ]
  ],
  "openalex": "W7211928295",
  "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014749&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/503z46m8zwh6n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.pcbi.1014749",
      "source": "plos",
      "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014749"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression",
  "title_text": "Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/503z46m8zwh6n",
  "venue": "PLOS Computational Biology",
  "versions": []
}