2. Academic Validation
  3. Promoter Hyper-methylation of ZNF662 Restrains its Tumor Suppressing Function in Triple-Negative Breast Cancer Through Regulating NGF Signaling Axis

Promoter Hyper-methylation of ZNF662 Restrains its Tumor Suppressing Function in Triple-Negative Breast Cancer Through Regulating NGF Signaling Axis

  • Int J Biol Sci. 2025 Jun 12;21(9):4081-4097. doi: 10.7150/ijbs.102940.
Renjie Yu 1 2,  Xi Peng 1,  Zhaobo Cheng 1,  Yue Wu 1,  Huan Rong 2,  Lin Yi 1,  Jing Ran 2,  Chaoqun Deng 1,  Xiangyi Zhou 1,  Ruijie Ming 1,  Ningning Zhang 2,  Xiaoyu Liu 2,  Xiaohua Zeng 2,  Yun Xiao 3,  Xue Wang 1 4,  Yongzhong Wu 2,  Bo Qin 1,  Tingxiu Xiang 1 2
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 2 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China.
  • 3 Department of Oncology and Hematology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
  • 4 The People's Hospital of Tongnan District Chongqing City, Chongqing, 402660, China.
PMID: 40612670 DOI: 10.7150/ijbs.102940
Abstract

Triple-negative breast Cancer (TNBC) has the highest mortality rate among common cancers in women. Thus, the identification of new therapeutic targets is of major significance. Our study identifies ZNF662 as a novel member of KRAB-containing zinc finger proteins (KRAB-ZFPs) family in TNBC. However, its biological function and potential mechanisms in the progression of TNBC have not been clarified. We found that down-regulation of ZNF662 in breast Cancer was associated with abnormal promoter methylation. ZNF662 over-expression inhibited triple-negative breast Cancer cell proliferation, migration and invasion and induced cell cycle arrest in vitro, and also suppressed the growth and metastasis of xenograft tumors in vivo. Further experiments confirmed that ZNF662 could directly bind to the NGF promoter sites and significantly inhibit NGF transcription activity. In addition, ZNF662 could increase the sensitivity of TNBC cells to the EGFR Inhibitor lapatinib. Molecular mechanisms revealed that ZNF662 affected downstream PI3K/Akt and STAT3 signaling pathways to inhibit TNBC progression by down-regulating NGF expression. Altogether, we speculated that ZNF662 might become a promising prognostic marker and therapeutic target for early detection and treatment of TNBC.

Keywords

NGF; ZNF662; methylation; transcription factor; triple-negative breast cancer.

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