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Objective <p>Testicular germ cell tumors (TGCTs), the most prevalent malignancy in males aged 15–40 years, exhibit suboptimal prognosis despite therapeutic advances. This study aimed to identify novel diagnostic biomarkers and elucidate their molecular mechanisms in TGCTs pathogenesis.</p> Methods <p>Through integrated bioinformatics analysis of public TCGA(The Cancer Genome Atlas)datasets and clinical specimen validation (<i>n</i> = 14), we screened LINC01272 as a candidate biomarker. RNA immunoprecipitation (RIP) assays were employed to verify the interaction between LINC01272 and fused in sarcoma (FUS). Functional experiments including siRNA-mediated gene silencing, transwell migration/invasion assays, and CCK-8 proliferation tests were performed in TGCTs cell lines (Tcam-2 and NCCIT).</p> Results <p>LINC01272 is significantly highly expressed in TGCT tissues. High LINC01272 levels indicate shorter overall and recurrence-free survival periods for patients; the predictive value is particularly significant in the subgroup with low tumor mutation burden. Silencing LINC01272 can inhibit the migration, invasion and proliferation of Tcam-2 and NCCIT cells, and down-regulate N-cadherin and Vimentin, while up-regulating LAMA1. RIP assays confirmed the direct binding of LINC01272 to FUS. FUS silencing can replicate the tumor suppressive effect of LINC01272 deletion, while FUS overexpression can reverse the inhibition of migration, invasion and proliferation caused by LINC01272 silencing.</p> Conclusion <p>We identified the LINC01272-FUS axis as a critical regulatory pathway in TGCTs progression, providing mechanistic insights for developing liquid biopsy biomarkers and RNA-targeted therapies.</p>

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Targeting the LINC01272-FUS signal axis inhibits the migration and invasion of testicular germ cell tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月12日

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  • Xueheng Zhao,
  • Jian Cao,
  • Lei Xue,
  • Liqing Fan,
  • Fang Zhu,
  • Zailong Qin,
  • Ziyi Chen,
  • Zhizhong Liu,
  • Jinhui Shu,
  • Hao Bo

摘要

Objective

Testicular germ cell tumors (TGCTs), the most prevalent malignancy in males aged 15–40 years, exhibit suboptimal prognosis despite therapeutic advances. This study aimed to identify novel diagnostic biomarkers and elucidate their molecular mechanisms in TGCTs pathogenesis.

Methods

Through integrated bioinformatics analysis of public TCGA(The Cancer Genome Atlas)datasets and clinical specimen validation (n = 14), we screened LINC01272 as a candidate biomarker. RNA immunoprecipitation (RIP) assays were employed to verify the interaction between LINC01272 and fused in sarcoma (FUS). Functional experiments including siRNA-mediated gene silencing, transwell migration/invasion assays, and CCK-8 proliferation tests were performed in TGCTs cell lines (Tcam-2 and NCCIT).

Results

LINC01272 is significantly highly expressed in TGCT tissues. High LINC01272 levels indicate shorter overall and recurrence-free survival periods for patients; the predictive value is particularly significant in the subgroup with low tumor mutation burden. Silencing LINC01272 can inhibit the migration, invasion and proliferation of Tcam-2 and NCCIT cells, and down-regulate N-cadherin and Vimentin, while up-regulating LAMA1. RIP assays confirmed the direct binding of LINC01272 to FUS. FUS silencing can replicate the tumor suppressive effect of LINC01272 deletion, while FUS overexpression can reverse the inhibition of migration, invasion and proliferation caused by LINC01272 silencing.

Conclusion

We identified the LINC01272-FUS axis as a critical regulatory pathway in TGCTs progression, providing mechanistic insights for developing liquid biopsy biomarkers and RNA-targeted therapies.