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Peer-reviewedCC BY-NC-NDBMC cancer

NaB-induced inhibition of HDAC4 and TUG1: a novel strategy for reversing oxaliplatin resistance in colorectal cancer.

  • Wang Yingchen1,2,3
  • Wu Yinhang1,2,3
  • Zhuang Jing1,2,3
  • Chu Jian1,2,3
  • Wu Zheng1,2,3
  • Liu Jiang4,5,6
  • Han Shuwen7,8,9,10,11
11 affiliations
  1. 1Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang Province, People's Republic of China.
  2. 2Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, People's Republic of China.
  3. 3Zhejiang-France United Laboratory of Integrated Traditional Chinese and Modern Medicine in Colorectal Cancer, Huzhou, Zhejiang Province, People's Republic of China.
  4. 4Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang Province, People's Republic of China. [email protected].
  5. 5Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, People's Republic of China. [email protected].
  6. 6Zhejiang-France United Laboratory of Integrated Traditional Chinese and Modern Medicine in Colorectal Cancer, Huzhou, Zhejiang Province, People's Republic of China. [email protected].
  7. 7Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang Province, People's Republic of China. [email protected].
  8. 8School of Medicine, Tarim University, Alaer, Xinjiang, 843300, People's Republic of China. [email protected].
  9. 9Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558 Sanhuan North Road, Wuxing District, Huzhou, Zhejiang Province, 313000, People's Republic of China. [email protected].
  10. 10Zhejiang-France United Laboratory of Integrated Traditional Chinese and Modern Medicine in Colorectal Cancer, Huzhou, Zhejiang Province, People's Republic of China. [email protected].
  11. 11ASIR (Institute - Association of intelligent systems and robotics), 14B rue Henri Sainte Claire Deville, Rueil-Malmaison, 92500, France. [email protected].
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Abstract

Background

Oxaliplatin (OXA) resistance affects the efficacy of colorectal cancer (CRC) treatment.Methods

Gene expression profiles of OXA-resistant and OXA-sensitive cells were compared to identify differentially expressed non-coding RNAs. A dual-luciferase assay was used to research the targeting relationship and binding region of TUG1 and miR-449a. SiRNA interference was used to construct cell models of OXA-resistant cells with low expression of TUG1 and OXA-sensitive cells with high expression of HDAC, as well as animal models based on these two types of cells. Then, cellular function was assessed. Histopathologic conditions were assessed by immunohistochemistry.Results

TUG1, miR-449a and Histone Deacetylase 4 (HDAC4) were all upregulated in OXA-resistant cells, and the increase of HDAC4 was accompanied by a decrease in acetylation level. TUG1 binds to miR-449a, and TUG1 was located in the cytoplasm of OXA-resistant cells. Downregulated expression of TUG1 could inhibit proliferation and induce apoptosis in OXA-resistant cells and reverse OXA resistance. Downregulated expression of HDAC4 could reduce the expression of TUG1, and inhibit proliferation and induce apoptosis of OXA-resistant cells. Treatment with 2 mmol/L sodium butyrate (NaB), a histone deacetylase inhibitor, markedly suppressed tumor cell growth through regulation of TUG1 compared with 0.01 mmol/L NaB. The OXA-resistant tumor-bearing mouse experiment further confirmed the inhibitory effect of NaB on tumor.Conclusion

High-dose NaB can inhibit the expression of HDAC4, and then reduce the expression of TUG1 through acetylation modification, thereby inhibiting the development of CRC and reversing OXA resistance in CRC.

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Cite

BibTeXRIS
BibTeX
@article{yingchen2026nabinduced,
  title = {{NaB-induced inhibition of HDAC4 and TUG1: a novel strategy for reversing oxaliplatin resistance in colorectal cancer.}},
  author = {Wang Yingchen and Wu Yinhang and Zhuang Jing and Chu Jian and Wu Zheng and Liu Jiang and Han Shuwen},
  journal = {BMC cancer},
  year = {2026},
  month = nov,
  doi = {10.1186/s12885-026-16367-7},
  url = {https://europepmc.org/article/MED/42972541},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - NaB-induced inhibition of HDAC4 and TUG1: a novel strategy for reversing oxaliplatin resistance in colorectal cancer.
AU  - Wang Yingchen
AU  - Wu Yinhang
AU  - Zhuang Jing
AU  - Chu Jian
AU  - Wu Zheng
AU  - Liu Jiang
AU  - Han Shuwen
PY  - 2026
DA  - 2026/11/03
JO  - BMC cancer
DO  - 10.1186/s12885-026-16367-7
UR  - https://europepmc.org/article/MED/42972541
AB  - Background  Oxaliplatin (OXA) resistance affects the efficacy of colorectal cancer (CRC) treatment.Methods  Gene expression profiles of OXA-resistant and OXA-sensitive cells were compared to identify differentially expressed non-coding RNAs. A dual-luciferase assay was used to research the targeting relationship and binding region of TUG1 and miR-449a. SiRNA interference was used to construct cell models of OXA-resistant cells with low expression of TUG1 and OXA-sensitive cells with high expression of HDAC, as well as animal models based on these two types of cells. Then, cellular function was assessed. Histopathologic conditions were assessed by immunohistochemistry.Results  TUG1, miR-449a and Histone Deacetylase 4 (HDAC4) were all upregulated in OXA-resistant cells, and the increase of HDAC4 was accompanied by a decrease in acetylation level. TUG1 binds to miR-449a, and TUG1 was located in the cytoplasm of OXA-resistant cells. Downregulated expression of TUG1 could inhibit proliferation and induce apoptosis in OXA-resistant cells and reverse OXA resistance. Downregulated expression of HDAC4 could reduce the expression of TUG1, and inhibit proliferation and induce apoptosis of OXA-resistant cells. Treatment with 2 mmol/L sodium butyrate (NaB), a histone deacetylase inhibitor, markedly suppressed tumor cell growth through regulation of TUG1 compared with 0.01 mmol/L NaB. The OXA-resistant tumor-bearing mouse experiment further confirmed the inhibitory effect of NaB on tumor.Conclusion  High-dose NaB can inhibit the expression of HDAC4, and then reduce the expression of TUG1 through acetylation modification, thereby inhibiting the development of CRC and reversing OXA resistance in CRC.
SN  - 1471-2407
ER  -