4.7 Article

LINC00313 regulates the metastasis of testicular germ cell tumors through epithelial-mesenchyme transition and immune pathways

Journal

BIOENGINEERED
Volume 13, Issue 5, Pages 12141-12155

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2022.2073128

Keywords

Testicular germ cell tumor; TGCT; LINC00313; migration; invasion; immune

Funding

  1. Changsha Municipal Natural Science Foundation [kq2014033]
  2. Natural Science Foundation of Hunan Province [2021JJ41091]
  3. Guangzhou Municipal/University (High-Level University) [202102010055]
  4. Guangdong Basic and Applied Basic Research Foundation [2019A1515010755]
  5. Medical Key Discipline of Guangzhou (2021-2023)
  6. National Natural Science Foundation of China [82001634]
  7. China Postdoctoral Science Foundation [2019M661521]
  8. Hunan Provincial Grant for Innovative Province Construction [2019SK4012]
  9. Fundamental Research Funds for Health Commission of Hunan Province [C2019073]
  10. Natural Science Foundation of Changsha Science and Technology Bureau [kq2004134]
  11. Wu Jie-PingMedical Foundation [320.6750.2020-14-14]

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Testicular germ cell tumor (TGCT) is a relatively rare tumor but the most common solid tumor in young men. LINC00313, a long noncoding RNA, plays important roles in promoting migration and invasion in TGCT through regulating the expression of epithelial-mesenchyme transition related proteins. In addition, LINC00313 expression is negatively correlated with copy number variation and immune cell infiltration. Panobinostat shows potential as a drug targeting LINC00313 in TGCT.
Testicular germ cell tumor (TGCT) is a relatively rare entity tumor, accounting for only 1% of all male cancers. However, it is the most common solid tumor in young men between 15 and 34 years old. Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the functions of lncRNAs in TGCT have only rarely been investigated. LncRNAs associated with TGCT were identified using Gene Expression Omnibus (GEO) database and UCSC XENA database data mining. The effects of LINC00313 on NCCIT cell migration and invasion were evaluated in transwell assays. The expression levels of epithelial-mesenchyme transition (EMT)-related proteins in cells knockdown of LINC00313 were analyzed by Western blot. Correlation analyses between lncRNA LINC00313 expression and copy number variation (CNV) and immune cell infiltration were carried out using The Cancer Genome Atl as (TCGA) data. The effect of Panobinostatin targeting LINC00313 in TGCT cells was investigated. We observed higher LINC00313 expression in TGCT. The migratory and invasive properties of TGCT cells were augmented by LINC00313, likely via its effects on modulating the expression of epithelial-mesenchyme transition (EMT) related proteins: CTNNB1, ZEB1, CDH2, Snail and VIM. Moreover, LINC00313 expression and CNV correlated negatively with the infiltration of immune cells. In addition, Panobinostat might be a possible candidate drug to target LINC00313 in TGCT. LINC00313 performs important pro-migration and invasion functions in the pathogenesis of TGCT. LINC00313 could be used as diagnostic, prognostic, immune marker and therapeutic target to develop effective treatment of TGCT.

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