---
title: "SCRMP drives cisplatin resistance in small cell lung cancer via CSNK2B SUMOylation and enhanced DN"
id: "pubmed-42777084"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42777084"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42777084/"
doi: "10.1126/scitranslmed.aea5653"
published_at: "2026-09-23T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SCRMP drives cisplatin resistance in small cell lung cancer via CSNK2B SUMOylation and enhanced DN
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42777084
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42777084/)
- **DOI:** [10.1126/scitranslmed.aea5653](https://doi.org/10.1126%2Fscitranslmed.aea5653)
- **Published At:** 2026-09-23T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Small cell lung cancer (SCLC) frequently acquires resistance to platinum agents (cisplatin/carboplatin), undermining first-line therapy effectiveness. The molecular basis of this resistance is incompletely defined. - Multiomic integration (transcriptomics from cisplatin-resistant PDXs and the IMpower133 cohort plus translatomics from SCLC cells) identified a previously unannotated noncanonical open reading frame from MIR7-3HG that encodes a 128–amino-acid microprotein named **SCRMP** (SCLC cisplatin resistance-associated microprotein). - **SCRMP** expression was increased in cisplatin-resistant SCLC tissues and cell lines and associated with poorer platinum response and worse patient survival in the analyzed cohorts. - Functional loss of **SCRMP** using CRISPR-Cas9 restored cisplatin sensitivity and increased apoptosis in SCLC cell lines, platinum-resistant patient-derived organoids (PDOs) in vitro, and patient-derived xenografts (PDXs) in vivo. - Mechanistically, **SCRMP** promotes platinum resistance by mediating **SUMOylation** and nuclear translocation of **CSNK2B**. Nuclear CSNK2B stabilizes the **RBBP4–p300** complex, enhancing histone acetylation at target loci. - The stabilized RBBP4–p300 complex increases transcription of **RAD51C** and other DNA damage repair genes, thereby enhancing DNA repair capacity and facilitating resistance to platinum-induced DNA damage. - The study delineates a specific pathway linking a noncanonical microprotein to posttranslational modification of a kinase subunit, chromatin remodeling, and activation of homologous recombination–related repair genes as a mechanism of chemoresistance. - Findings provide a mechanistic basis for potential interventions targeting **SCRMP**, CSNK2B SUMOylation, or downstream chromatin/repair effectors to overcome platinum resistance in SCLC. Details on clinical translation or therapeutic agents were not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 23. # SCRMP-mediated SUMOylation of CSNK2B facilitates DNA damage repair to promote cisplatin resistance in small cell lung cancer [Yuli Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-2 "Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China."), [Qinnan Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Q&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Jiahao Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+J&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Ziwei Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Z&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Shaokun Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+S&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Peng Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+P&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Xiao Ke](https://pubmed.ncbi.nlm.nih.gov/?term=Ke+X&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Xuefei Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+X&cauthor_id=42777084)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-3 "Huzhou Centre Hospital, Affiliated Centre Hospital Huzhou University, Huzhou, Zhejiang Province, China."), [Ming Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+M&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Fengqi Nie](https://pubmed.ncbi.nlm.nih.gov/?term=Nie+F&cauthor_id=42777084)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-4 "Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China."), [Xianghua Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42777084)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#full-view-affiliation-5 "Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, China.") Affiliations Expand ### Affiliations * 1 Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China. * 2 Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China. * 3 Huzhou Centre Hospital, Affiliated Centre Hospital Huzhou University, Huzhou, Zhejiang Province, China. * 4 Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. * 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, China. * PMID: **42777084** * DOI: [ 10.1126/scitranslmed.aea5653 ](https://doi.org/10.1126/scitranslmed.aea5653) Item in Clipboard # SCRMP-mediated SUMOylation of CSNK2B facilitates DNA damage repair to promote cisplatin resistance in small cell lung cancer Yuli Chen et al. Sci Transl Med. 2026. Show details Display options Display options Format Abstract PubMed PMID Sci Transl Med Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sci+Transl+Med%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Sci+Transl+Med%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42777084/) . 2026 Sep 23;18(868):eaea5653. doi: 10.1126/scitranslmed.aea5653. Epub 2026 Sep 23. ### Authors [Yuli Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-2 "Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China."), [Qinnan Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Q&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Jiahao Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+J&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Ziwei Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+Z&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Shaokun Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+S&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Peng Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+P&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Xiao Ke](https://pubmed.ncbi.nlm.nih.gov/?term=Ke+X&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Xuefei Shi](https://pubmed.ncbi.nlm.nih.gov/?term=Shi+X&cauthor_id=42777084)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-3 "Huzhou Centre Hospital, Affiliated Centre Hospital Huzhou University, Huzhou, Zhejiang Province, China."), [Ming Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+M&cauthor_id=42777084)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-1 "Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China."), [Fengqi Nie](https://pubmed.ncbi.nlm.nih.gov/?term=Nie+F&cauthor_id=42777084)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-4 "Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China."), [Xianghua Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42777084)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42777084/#short-view-affiliation-5 "Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, China.") ### Affiliations * 1 Department of Oncology, Oncology Laboratory of Medical Science and Technology Innovation Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, Jiangsu Province, China. * 2 Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China. * 3 Huzhou Centre Hospital, Affiliated Centre Hospital Huzhou University, Huzhou, Zhejiang Province, China. * 4 Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. * 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, China. * PMID: **42777084** * DOI: [ 10.1126/scitranslmed.aea5653 ](https://doi.org/10.1126/scitranslmed.aea5653) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Small cell lung cancer (SCLC) represents the most lethal subtype of lung carcinoma. Platinum-based agents, such as cisplatin and carboplatin, remain the cornerstone of first-line therapy for patients with SCLC, whether administered as chemotherapy alone or in combination with immunotherapy. However, patients frequently develop platinum resistance within a short time frame, leading to therapeutic failure. The molecular mechanisms underlying platinum resistance in SCLC require further investigation, given that effective intervention strategies remain elusive. Through multiomic analysis integrating transcriptomic data from cisplatin-resistant PDX tissues and the IMpower133 SCLC cohort study and translatomic data from SCLC cells, we identified a platinum resistance-associated noncanonical open reading frame derived from _MIR7_ -_3HG_. This noncanonical ORF encodes an unannotated 128-amino acid protein, designated SCRMP (SCLC cisplatin resistance-associated microprotein). SCRMP was up-regulated in cisplatin-resistant SCLC tissues and cell lines, and its elevated expression strongly correlated with impaired platinum response and unfavorable survival outcomes in patients. CRISPR-Cas9-mediated _SCRMP_ knockout restored cisplatin sensitivity and promoted apoptosis in SCLC cells, platinum-resistant patient-derived organoids in vitro, and patient-derived xenografts in vivo. Mechanistically, SCRMP potentiated platinum resistance by mediating SUMOylation and nuclear translocation of CSNK2B, which stabilized the RBBP4-p300 complex. This stabilization activated transcription of RAD51C and associated DNA damage repair genes through histone acetylation, ultimately promoting therapeutic resistance. Our study systematically elucidates the biological function of SCRMP in SCLC platinum resistance and delineates its specific molecular mechanism in regulating DNA damage repair, thereby providing theoretical foundations and potential intervention strategies for overcoming platinum resistance in SCLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42777084/) * Apoptosis / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=
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