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Published on: April 7, 2017
LINC01518 functions as an oncogene in head and neck squamous cell carcinoma (HNSCC) by modulating miR-1-3p/Slug and
Swati1, Shraddha Tripathi1, Bakhya Shree1
1Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Telangana, 500078, India.
Abstract:
HNSCC is a highly aggressive cancer of the head and neck region, and there is an urgent need to find novel potential targets for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) have emerged as important therapeutic and diagnostic targets for multiple cancers, including HNSCC. LINC01518 promotes the proliferation of oesophageal cancer cells, but the involvement of LINC01518 in HNSCC pathophysiology is unknown. We show that LINC01518 expression is significantly upregulated in high-grade HNSCC tumor samples in comparison to normal tissue, and transforming growth factor- β (TGF-β) promotes LINC01518 expression in HNSCC cell lines. Loss-of-function studies suggest that LINC01518 promotes cell proliferation, migration, and invasion in HNSCC cells. In addition, LINC01518 depletion sensitizes HNSCC cells to cisplatin-mediated apoptosis. Mechanistically, LINC01518 acts as a competitive endogenous RNA and binds to miR-1-3p and miR-216b-5p, resulting in up-regulation of their target genes Slug and GRP78, respectively. Our findings suggest that LINC01518 is an attractive therapeutic target for HNSCC.
Insights
Long non-coding RNA LINC01518 promotes head and neck squamous cell carcinoma (HNSCC) progression and metastasis. Targeting LINC01518 may offer a novel therapeutic strategy for HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with limited therapeutic options.
- Long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators in cancer development and progression.
- The role of LINC01518 in HNSCC remains largely unexplored, despite its known function in other cancers.
Purpose of the Study:
- To investigate the role and mechanism of LINC01518 in the pathophysiology of HNSCC.
- To determine if LINC01518 could serve as a potential diagnostic or therapeutic target for HNSCC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess LINC01518 expression in HNSCC tissues and cell lines.
- In vitro loss-of-function experiments (siRNA-mediated knockdown) to evaluate the impact of LINC01518 on HNSCC cell behavior.
- Analysis of cell proliferation, migration, invasion, and apoptosis assays.
- RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to elucidate the molecular mechanism involving microRNAs (miRNAs).
Main Results:
- LINC01518 expression was significantly upregulated in high-grade HNSCC tumors compared to normal tissues.
- Transforming growth factor-β (TGF-β) was identified as a promoter of LINC01518 expression in HNSCC cells.
- LINC01518 knockdown suppressed HNSCC cell proliferation, migration, and invasion.
- LINC01518 depletion enhanced cisplatin-induced apoptosis in HNSCC cells.
- Mechanistically, LINC01518 functions as a competing endogenous RNA (ceRNA) by sponging miR-1-3p and miR-216b-5p, leading to the upregulation of their target genes, Slug and GRP78, respectively.
Conclusions:
- LINC01518 plays a crucial oncogenic role in HNSCC by promoting cell proliferation, migration, invasion, and chemoresistance.
- LINC01518 acts as a ceRNA for miR-1-3p and miR-216b-5p, influencing the expression of Slug and GRP78.
- LINC01518 represents a promising therapeutic target for HNSCC.
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