Biology subjects

Sun, X.-X.

Publications and source records attributed to Sun, X.-X..

4 recordsLinked to original sources

bioRxiv2026

Global mRNA 3'UTR lengthening in small-cell neuroendocrine carcinoma

Small-cell neuroendocrine carcinoma (SCNC) is a rare but highly malignant tumor subtype that primarily arises in the lung, also rarely in other organs, and as a consequence of treatment induced lineage transdifferentiation of prostate adenocarcinomas. The molecular convergence of SCNC across diverse tissues enables its identification through conserved SCNC-specific molecular markers, facilitating tumor subtype classification. As a critical post-transcriptional regulatory mechanism, alternative polyadenylation (APA) modulates 3'UTR length and significantly impacts tumor progression. However, its role in SCNC remains largely unclear. Here, we report a global 3'UTR lengthening pattern driven by APA in SCNC. We identified a set of conserved 3'UTR lengthening events across SCNCs of different tissue origins, which are strongly associated with neural development and related signaling pathways. Furthermore, we developed a neural network-based prediction model to classify SCNC by leveraging these specific APA signatures. Our study provides new insights into the post-transcriptional landscape of SCNCs and highlights APA signatures as promising biomarkers for SCNC identification.

cancer biology↗

bioRxiv2025

GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination

DNA double-strand break (DSB) repair via homologous recombination (HR) is critical for maintaining genomic integrity and requires proper DNA end resection to generate single-stranded DNA (ssDNA) overhangs. However, the mechanisms governing this critical step in cells remains poorly understood. Here, we report that GNL3, a nucleolar GTP-binding protein, plays a key role in HR repair via regulating DNA end resection dependently on its SUMOylation. Ectopic expression of wild-type, but not the SUMO-defective K196R mutant, GNL3 completely abolished DNA damage response induced by knockdown of endogenous GNL3. GNL3 interacts with the BLM-DNA2 helicase-nuclease complex and is critical for DNA end resection and subsequent loading of RPA and RAD51. This interaction requires SUMOylation and SUMO-interacting motifs (SIMs) in both proteins. We further demonstrate that USP36, a nucleolar deubiquitinating enzyme, functions as a novel SUMO ligase for GNL3, while the SUMO protease SENP3 deSUMOylates GNL3. Notably, several breast cancer-derived GNL3 variants that disrupt its SUMOylation or SIM fail to interact with the BLM-DNA2 complex. Knockdown of GNL3 sensitizes HR-proficient breast cancer cells to etoposide or Olaparib treatment. Together, our results reveal that GNL3 SUMOylation is crucial for HR repair and suggest that targeting GNL3 SUMOylation may induce HR deficiency, thereby sensitizing breast cancers to DNA damage-inducing agents.

cell biology↗

bioRxiv2025

MYC Serine 62 phosphorylation promotes its binding to DNA double strand breaks to facilitate repair and cell survival under genotoxic stress.

Genomic instability is a hallmark of cancer, driving oncogenic mutations that enhance tumor aggressiveness and drug resistance. MYC, a master transcription factor that is deregulated in nearly all human tumors, paradoxically induces replication stress and associated DNA damage while also increasing expression of DNA repair factors and mediating resistance to DNA-damaging therapies. Emerging evidence supports a non-transcriptional role for MYC in preserving genomic integrity at sites of active transcription and protecting stalled replication forks under stress. Understanding how MYCs genotoxic and genoprotective functions diverge may reveal new therapeutic strategies for MYC-driven cancers. Here, we identify a non-canonical role of MYC in DNA damage response (DDR) through its direct association with DNA breaks. We show that phosphorylation at serine 62 (pS62-MYC) is crucial for the efficient recruitment of MYC to damage sites, its interaction with repair factors BRCA1 and RAD51, and effective DNA repair to support cell survival under stress. Mass spectrometry analysis with MYC-BioID2 during replication stress reveals a shift in MYCs interactome, maintaining DDR associations while losing transcriptional regulators. These findings establish pS62-MYC as a key regulator of genomic stability and a potential therapeutic target in cancers.

cancer biology↗

bioRxiv2020

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

microbiology↗