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<p>Tubulin tyrosine ligase-like enzyme-12 (TTLL-12), belonging to the TTLL family, holds a crucial position in posttranslational tubulin modifications implicated in cancer development, making it a potential target for anti-tumor therapy. However, the precise mechanisms of TTLL12 in HCC remain inadequately elucidated. In this study, we found markedly elevated expression of TTLL12 in HCC tissues compared to their adjacent normal counterparts, which is strongly linked to an unfavorable prognosis. Functional assays demonstrated that knockdown of TTLL12 significantly suppressed HCC cell proliferation, whereas overexpression of TTLL12 promoted oncogenic behaviors. In vivo models further confirmed that TTLL12 enhances tumor growth, as indicated by larger tumors in TTLL12-overexpressing cells compared to vector controls. Mechanistically, TTLL12 suppressed ubiquitin-proteasome-mediated degradation of eEF1A1 via competing with Bood POZ-containing gene type 2 (BPOZ-2), which typically recruits eEF1A1 to CULLIN (CUL3), and ultimately results in an enhancement of cancer cell proliferation. Our analyses underscore the oncogenic potential of TTLL12 in hepatocarcinogenesis by safeguarding eEF1A1 from BPOZ-2- mediated degradation, introducing a novel therapeutic target for combating HCC.</p>

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TTLL12 counteracts BPOZ-2 to stabilize eEF1A1 and promote hepatocarcinogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Kaiming Leng,
  • Zhen Yang,
  • Yao Liming,
  • Nanfeng Meng,
  • Yi Xu,
  • Guanqun Liao,
  • Mei Han,
  • Guangjun Shi

摘要

Tubulin tyrosine ligase-like enzyme-12 (TTLL-12), belonging to the TTLL family, holds a crucial position in posttranslational tubulin modifications implicated in cancer development, making it a potential target for anti-tumor therapy. However, the precise mechanisms of TTLL12 in HCC remain inadequately elucidated. In this study, we found markedly elevated expression of TTLL12 in HCC tissues compared to their adjacent normal counterparts, which is strongly linked to an unfavorable prognosis. Functional assays demonstrated that knockdown of TTLL12 significantly suppressed HCC cell proliferation, whereas overexpression of TTLL12 promoted oncogenic behaviors. In vivo models further confirmed that TTLL12 enhances tumor growth, as indicated by larger tumors in TTLL12-overexpressing cells compared to vector controls. Mechanistically, TTLL12 suppressed ubiquitin-proteasome-mediated degradation of eEF1A1 via competing with Bood POZ-containing gene type 2 (BPOZ-2), which typically recruits eEF1A1 to CULLIN (CUL3), and ultimately results in an enhancement of cancer cell proliferation. Our analyses underscore the oncogenic potential of TTLL12 in hepatocarcinogenesis by safeguarding eEF1A1 from BPOZ-2- mediated degradation, introducing a novel therapeutic target for combating HCC.