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CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review)

  • Authors:
    • Xiaoying Zhao
    • Wenjing Zhang
    • Xiang Yu
    • Xiaohan Zhao
    • Xu Dai
    • Sirui Chen
    • Yan Wang
    • Jiang Cheng
    • Weiwei Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832008, P.R. China, Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China, First School of Clinical Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China, School of Clinical Medicine, Xinjiang Second Medical College, Karamay, Xinjiang Uygur Autonomous Region 834000, P.R. China, School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China, Department of Laboratory Medicine, Wenjiang District People's Hospital of Chengdu, Chengdu, Sichuan 611100, P.R. China
  • Article Number: 23
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    Published online on: December 16, 2025
       https://doi.org/10.3892/ijo.2025.5836
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Abstract

The present study focused on the role of coiled‑coil domain‑containing protein 137 (CCDC137), an RNA‑binding and epigenetic protein with high expression and poor prognosis in various types of cancer. Bioinformatics analysis, cellular experiments and animal models investigated the functions of CCDC137 in RNA post‑transcriptional regulation, epigenetic modification and the tumor microenvironment. The results showed that CCDC137 can bind specific mRNAs to affect physiological processes such as the cell cycle, participate in epigenetic regulation such as DNA methylation and histone modification and influence tumor immune escape by affecting the functions of tumor‑associated macrophages. Based on the multidimensional regulatory functions of CCDC137, it is expected to become a new target for cancer diagnosis and treatment and provide a theoretical basis for precision cancer therapy.
View Figures

Figure 1

Structure of CCDC137. Three
dimensional structures from AlphaFold (predicted) for CCDC137
Gene.

Figure 2

The roles of CCDC family types of
cancer. The CCDC family exhibits varied tumor-regulatory roles. In
lung adenocarcinoma, CCDC65 recruits FBXW7 to degrade c-Myc and
ENO1, inhibiting cell cycle signaling. In gastric cancer, CCDC65
degrades ENO1, reduces AKT1 phosphorylation, and suppresses cell
cycle and EMT signaling. In thyroid cancer, CCDC67 induces
apoptosis and inhibits metastasis by blocking G1/S
transition. In ovarian cancer, CCDC98 regulates BRCA1 dependent DNA
damage response. In colorectal cancer, CCDC68 downregulation
promotes CDK4 degradation, inhibiting G0/G1
transition. CCDC154 overexpression blocks G2/M phase,
while CCDC60 and CCDC110 induce G0/G1 and
G2/M arrests in head and neck squamous cell carcinoma
and osteosarcoma, respectively. These findings highlight the
potential role of CCDC137 in the tumor microenvironment. CCDC,
coiled-coil domain-containing protein; FBXW7, F-Box and WD repeat
domain containing 7; c-Myc, cellular Myelocytomatosis; ENO1,
enolase 1; EMT, epithelial-mesenchymal transition; BRCA1, breast
cancer gene 1; CDK4, cyclin-dependent kinase 4; HNSCC, head and
neck squamous cell carcinoma; RAP80, receptor-associated protein
80; RxRa, retinoid X receptor α, Cdc2, cell division cycle 2;
U2-OS, U-2 osteosarcoma.

Figure 3

Targeted CCDC137 therapy. Peptides
targeting CCDC137-LZTS2 binding, designed via computational
methods, inhibit tumor growth and metastasis with minimal side
effects, showing synergy with immune checkpoint inhibitors. CCDC137
activates β-catenin and AKT pathways, promoting cancer; inhibitors
such as ipatasertib and niclosamide target these pathways for
therapy. CCDC137 is enriched in cell cycle pathways
(G1/S; G2/M) across cancers such as glioma,
liver and lung, predicting poorer survival. In colorectal cancer,
CCDC137 enhances proliferation and metastasis via CDK12, while
CCDC68 inhibits growth through the RXRα/ITCH/CDK4 axis. Targeting
CDK12 or cyclins offers potential anticancer strategies. CCDC,
coiled-coil domain containing protein.

Figure 4

The multiple biological functions of
CCDC137. CCDC137, a coiled-coil protein, is highly expressed in HCC
and CRC, promoting tumor proliferation, metastasis and poor
prognosis. It activates β-catenin and AKT pathways via LZTS2 and
β-TrCP interactions and regulates mRNA localization (FOXM1, JTV1,
LASP1, FLOT2) through DGCR8 binding. In CRC, CDK12 enhances CCDC137
expression via SEs, promoting liver metastasis. Upregulation of
CCDC137 in breast cancer involves SEs and promoter hypomethylation,
forming an oncogenic network. Its role in cell cycle regulation,
particularly G2/M arrest and RNA-epigenetic synergy
suggests CCDC137 as a promising therapeutic target, though specific
binding mechanisms remain unclear. CCDC137, coiled-coil domain
containing 137; LZTS2, leucine zipper tumor suppressor 2; β-TrCP,
beta-transducin repeat containing E3 ubiquitin protein ligase;
FOXM1, Forkhead box M1; JTV1 (ARS2), arsenite resistance protein 2;
LASP1, LIM and SH3 protein 1; FLOT2, flotillin 2; DGCR8, DiGeorge
Syndrome critical region gene 8; CDK12, cyclin dependent kinase 12;
Ses, super enhancers.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao X, Zhang W, Yu X, Zhao X, Dai X, Chen S, Wang Y, Cheng J and Zheng W: CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review). Int J Oncol 68: 23, 2026.
APA
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S. ... Zheng, W. (2026). CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review). International Journal of Oncology, 68, 23. https://doi.org/10.3892/ijo.2025.5836
MLA
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S., Wang, Y., Cheng, J., Zheng, W."CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review)". International Journal of Oncology 68.2 (2026): 23.
Chicago
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S., Wang, Y., Cheng, J., Zheng, W."CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review)". International Journal of Oncology 68, no. 2 (2026): 23. https://doi.org/10.3892/ijo.2025.5836
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao X, Zhang W, Yu X, Zhao X, Dai X, Chen S, Wang Y, Cheng J and Zheng W: CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review). Int J Oncol 68: 23, 2026.
APA
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S. ... Zheng, W. (2026). CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review). International Journal of Oncology, 68, 23. https://doi.org/10.3892/ijo.2025.5836
MLA
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S., Wang, Y., Cheng, J., Zheng, W."CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review)". International Journal of Oncology 68.2 (2026): 23.
Chicago
Zhao, X., Zhang, W., Yu, X., Zhao, X., Dai, X., Chen, S., Wang, Y., Cheng, J., Zheng, W."CCDC137: A key hub for RNA and epigenetic regulation in cancer research (Review)". International Journal of Oncology 68, no. 2 (2026): 23. https://doi.org/10.3892/ijo.2025.5836
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