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Published on: May 30, 2025
The long noncoding RNA LINC00341 suppresses colorectal carcinoma by preventing cell migration and apoptosis
Shuyuan Li1, Shuo Chen1, Boxue Wang1
1Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
Abstract:
Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies.
Insights
Long noncoding RNA 341 (LINC00341) is downregulated in colorectal cancer, hindering apoptosis and promoting cell migration. Restoring LINC00341 levels may offer a new therapeutic strategy for this malignancy.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Long noncoding RNAs (lncRNAs) regulate gene expression and are implicated in oncogenesis.
- The functions of most lncRNAs, including their roles in colorectal carcinoma (CRC), remain largely unexplored.
- Aberrant lncRNA expression is a known driver of tumor development.
Purpose of the Study:
- To investigate the role of the novel lncRNA LINC00341 in colorectal carcinoma.
- To elucidate the molecular mechanisms by which LINC00341 influences CRC progression.
- To identify potential therapeutic targets for CRC based on lncRNA function.
Main Methods:
- Microarray-based screening of CRC specimens to identify differentially expressed lncRNAs.
- Functional assays including overexpression and silencing of LINC00341 in CRC cells.
- RNA-pulldown assays to identify binding partners of LINC00341.
- Analysis of HMGB2 localization and its impact on epithelial-mesenchymal transition (EMT).
Main Results:
- LINC00341 was found to be aberrantly downregulated in metastatic CRC.
- LINC00341 overexpression suppressed tumor growth and promoted apoptosis, while silencing accelerated proliferation and migration.
- LINC00341 physically binds to HMGB2, stabilizing its cytoplasmic localization.
- LINC00341 knockdown caused HMGB2 nuclear translocation, triggering EMT.
Conclusions:
- LINC00341 acts as a tumor suppressor in colorectal carcinoma by inhibiting migration and promoting apoptosis.
- The LINC00341-HMGB2 interaction is crucial for preventing EMT and maintaining tumor suppression.
- This study reveals a novel lncRNA-mediated regulatory network with potential therapeutic implications for CRC.
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