ArticleSignal transduction and targeted therapy2022
RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- The long non-coding RNA-encoded microprotein MKKS3 drives colorectal cancer chemoresistance.Experimental & molecular medicine · 2026Article
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- Novel Susceptibility Genes for Sepsis Revealed by a Cross-Tissue Transcriptome-Wide Association Study.Shock (Augusta, Ga.) · 2026Article
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- RNA-binding protein BICC1 promotes gastric cancer progression via the PRRX1-MAPK signaling axis.Functional & integrative genomics · 2026Article
- Subtype-Specific mInternational journal of molecular sciences · 2026Article
- mFrontiers in cell and developmental biology · 2026Review
- Circ72688 Drives Breast Cancer Invasion and Metastasis via the miR-654-5p/ORAI2 Axis.Oncology research · 2026Article
- ZCCHC4 Orchestrates Hepatocellular Carcinoma Metastasis by Regulating Lipid biosynthesis and TMEM97/LCN2/Twist1 Pathway.International journal of biological sciences · 2026Article
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- Long non-coding RNA in hepatocellular carcinoma: mechanistic insights and therapeutic perspectives.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Lactylation in cancer: Advances and opportunities for treatment resistance.Clinical and translational medicine · 2025Review
- Emerging role of RNA m6A modifications in laryngeal squamous cell carcinoma: insights into tumorigenesis and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Review
- Integrated pan-cancer analysis of RNA binding protein HuR investigates its biomarker potential in prognosis, immunotherapy, and drug sensitivity.PLoS computational biology · 2025Article
- LncRNA TMPO-AS1 facilitates cervical cancer cell tumorigenesis and ferroptosis resistance via interaction with LCN2.Scientific reports · 2025Article
- The role of RNA binding proteins in cancer biology: A focus on FMRP.Genes & diseases · 2025Review
- The dual role of RNA-binding proteins: promotion of tumorigenesis, drug resistance, and emerging therapeutic targets.Acta biochimica et biophysica Sinica · 2025Article
- hnRNPH1: A Multifaceted Regulator in RNA Processing and Disease Pathogenesis.International journal of molecular sciences · 2025Review
- A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma.Molecular biotechnology · 2025Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-binding proteins (RBPs) play important roles in cancer development and treatment. However, the tumor-promoting RBPs and their partners, which may potentially serve as the cancer therapeutic targets, need to be further identified. Here, we report that zinc finger CCHC domain-containing protein 4 (ZCCHC4) is of aberrantly high expression in multiple human cancer tissues and is associated with poor prognosis and chemoresistance in patients of hepatocellular carcinoma (HCC), pancreatic cancer and colon cancer. ZCCHC4 promotes chemoresistance of HCC cells to DNA-damage agent (DDA) both in vitro and in vivo. HCC cell deficiency of ZCCHC4 reduces tumor growth in vivo and intratumoral interference of ZCCHC4 expression obviously enhances the DDA-induced antitumor effect. Mechanistically, ZCCHC4 inhibits DNA-damage-induced apoptosis in HCC cells by interacting with a new long noncoding RNA (lncRNA) AL133467.2 to hamper its pro-apoptotic function. Also, ZCCHC4 blocks the interaction between AL133467.2 and γH2AX upon DDA treatment to inhibit apoptotic signaling and promote chemoresistance to DDAs. Knockout of ZCCHC4 promotes AL133467.2 and γH2AX interaction for enhancing chemosensitivity in HCC cells. Together, our study identifies ZCCHC4 as a new predictor of cancer poor prognosis and a potential target for improving chemotherapy effects, providing mechanistic insights to the roles of RBPs and their partners in cancer progression and chemoresistance.
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