2. Academic Validation
  3. CDCA8 induced by NF-YA promotes hepatocellular carcinoma progression by regulating the MEK/ERK pathway

CDCA8 induced by NF-YA promotes hepatocellular carcinoma progression by regulating the MEK/ERK pathway

  • Exp Hematol Oncol. 2023 Jan 13;12(1):9. doi: 10.1186/s40164-022-00366-y.
Erbao Chen # 1 2,  Yu He # 2,  Jing Jiang # 3,  Jing Yi 1,  Zhilin Zou 4,  Qiuzi Song 1,  Qingqi Ren 1,  Zewei Lin 1,  Yi Lu 5 6,  Jikui Liu 7,  Jian Zhang 8 9
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China.
  • 2 School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
  • 3 Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
  • 4 Department of Ophthalmology, Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 5 School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. luy3@sustech.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen, Guangdong, China. luy3@sustech.edu.cn.
  • 7 Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China. liu8929@126.com.
  • 8 School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China. zhangjian@sustech.edu.cn.
  • 9 Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen, Guangdong, China. zhangjian@sustech.edu.cn.
  • # Contributed equally.
PMID: 36639822 DOI: 10.1186/s40164-022-00366-y
Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors. Cell division cycle associated 8 (CDCA8) is an important multifactorial regulator in cancers. However, its up and downstream targets and effects in HCC are still unclear.

Methods: A comprehensive bioinformatics analysis was performed using The Cancer Genome Atlas dataset (TCGA) to explore novel core oncogenes. We quantified CDCA8 levels in HCC tumors using qRT-PCR. HCC cell's proliferative, migratory, and invasive abilities were detected using a Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, clone formation, and a Transwell assay. An orthotopic tumor model and tail vein model were constructed to determine the effects of CDCA8 inhibition in vivo. The mechanism underlying CDCA8 was investigated using RNA Sequencing. The prognostic value of CDCA8 was assessed with immunohistochemical staining of the tissue microarrays.

Results: CDCA8 was identified as a novel oncogene during HCC development. The high expression of CDCA8 was an independent predictor for worse HCC outcomes both in publicly available datasets and in our cohort. We found that CDCA8 knockdown inhibited HCC cell proliferation, colony formation, and migration by suppressing the MEK/ERK pathway in vitro. Moreover, CDCA8 deficiency significantly inhibited tumorigenesis and metastasis. Next-generation Sequencing and laboratory validation showed that CDCA8 silencing inhibited the expression of TPM3, NECAP2, and USP13. Furthermore, NA-YA overexpression upregulated the expression of CDCA8. CDCA8 knockdown could attenuate NF-YA-mediated cell invasion in vitro. The expression of NF-YA alone or in combined with CDCA8 were validated as significant independent risk factors for patient survival.

Conclusion: Our findings revealed that the expression of CDCA8 alone or in combined with NF-YA contributed to Cancer progression, and could serve as novel potential therapeutic targets for HCC patients.

Keywords

Cancer metastasis; Cell division cycle associated 8; Hepatocellular carcinoma; NF-YA; Prognosis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50846
    98.97%, ERK1/2 Inhibitor
    ERK