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CCDC113 通过 TGF-β 信号通路促进结直肠癌的发生和转移。

CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-β signaling pathway.

机构信息

Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Cell Death Dis. 2024 Sep 11;15(9):666. doi: 10.1038/s41419-024-07036-3.

DOI:10.1038/s41419-024-07036-3
PMID:39261464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390942/
Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients' survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients' poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-β signaling pathway. TGF-β signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-β signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.

摘要

结直肠癌（CRC）是全球癌症相关死亡的第二大主要原因。尽管手术切除和免疫疗法改善了 CRC 患者的生存，但转移和复发仍然是导致预后不良的主要问题。因此，探索发病机制和识别特定的生物标志物对于 CRC 的早期诊断和靶向治疗至关重要。CCDC113 是 CCDC 家族的成员之一，据报道它在纤毛组装、纤毛活性、PSCI、哮喘和早期肺癌诊断中发挥作用。然而，CCDC113 在 CRC 中的功能仍不清楚。在本研究中，我们发现 CCDC113 在 CRC 中表达显著升高。CCDC113 的高表达与 CRC 患者的不良预后显著相关。CCDC113 是 CRC 肿瘤发生和转移所必需的。RNA-seq 和 TCGA 数据库分析表明，CCDC113 与 TGF-β 信号通路呈正相关。TGF-β 信号通路抑制剂 galunisertib 可以逆转 CCDC113 过表达在体外和体内引起的 CRC 细胞增殖和迁移能力的增加。这些结果表明，CCDC113 通过 TGF-β 信号通路促进 CRC 肿瘤发生和转移。总之，这是首次探索 CCDC113 在 CRC 肿瘤发生和转移中的功能和机制。CCDC113 可能是 CRC 干预的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/74bba3a2e37b/41419_2024_7036_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/cc3889811720/41419_2024_7036_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/e2fffbf3a727/41419_2024_7036_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/418dc4f39955/41419_2024_7036_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/9b232be77c49/41419_2024_7036_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/91962144ab90/41419_2024_7036_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/0bdfa3bfec55/41419_2024_7036_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/d4d2eac87997/41419_2024_7036_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/74bba3a2e37b/41419_2024_7036_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/cc3889811720/41419_2024_7036_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/e2fffbf3a727/41419_2024_7036_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/418dc4f39955/41419_2024_7036_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/9b232be77c49/41419_2024_7036_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/91962144ab90/41419_2024_7036_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/0bdfa3bfec55/41419_2024_7036_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/d4d2eac87997/41419_2024_7036_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e906/11390942/74bba3a2e37b/41419_2024_7036_Fig8_HTML.jpg

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