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Loc646329 sponges miR-21 to reduce RAS/MAP kinase signaling pathway in oral squamous cell carcinoma (OSCC)
Akhtar Adereh1, Parya Amini2, Azadeh Fateh3
1Yasuj University of Medical Science, Yasuj, Iran.
Abstract:
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer. Emerging evidence suggests that microRNAs (miRNAs) play a crucial role in the development and progression of OSCC. In particular, miR-21 has been implicated in various cellular processes, including proliferation, apoptosis, and invasion; it could be a potential therapeutic target for OSCC. In this study, The Cancer Genome Atlas (TCGA) for OSCC (TCGA-OSCC) clinical information was used. Patient outcomes were analyzed through survival analysis using Kaplan-Meier curves and log-rank tests. The HSC-3cell line was used as the OSCC cell line, which is known for its aggressive characteristics. The expression of Loc646329, miR-21, PTEN, PDCD4, and SPRY2 was evaluated by RT-PCR, flow cytometry, and scratch assay. Also, the effect of Loc646329 expression on OSCC was evaluated using the in vivo Xenograft Mouse Model. The results showed that overexpression of Loc646329 leads to the downregulation of miR-21, PDCD4, and SPRY2 genes while the PTEN gene is upregulated. In other words, the overexpression of Loc646329 by miR-21 inhibition (thorough targeting RAS/MAPK pathway) induces apoptosis and stops the cell cycle in OSCC cells. In vivo tests showed that elevated Loc646329 expression was linked to positive pathological outcomes, such as smaller tumor size, reduced lymph node metastasis, and enhanced overall survival in OSCC patients. In conclusion, the identification of Loc646329 as a sponge for miR-21 and its impact on the RAS/MAPK signaling pathway offers new opportunities for the development of innovative therapeutic strategies for OSCC. Further investigations into this regulatory axis may uncover additional targets for precision medicine approaches in the treatment of OSCC.
Insights
Loc646329 acts as a sponge for miR-21, inhibiting its activity and promoting apoptosis in oral squamous cell carcinoma (OSCC). Overexpression of Loc646329 correlates with improved patient outcomes and reduced tumor progression in OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited treatment options.
- MicroRNAs (miRNAs), such as miR-21, are increasingly recognized for their roles in OSCC development and progression.
- Identifying novel therapeutic targets is crucial for improving patient outcomes in OSCC.
Purpose of the Study:
- To investigate the role of Loc646329 as a potential regulator in OSCC.
- To explore the interaction between Loc646329 and miR-21 in OSCC.
- To evaluate the therapeutic potential of targeting the Loc646329-miR-21 axis in OSCC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) for OSCC clinical data and patient survival.
- In vitro studies using the HSC-3 OSCC cell line to assess gene expression (RT-PCR) and cellular behavior (flow cytometry, scratch assay).
- In vivo evaluation of Loc646329's effect on OSCC tumor growth and metastasis in a Xenograft Mouse Model.
Main Results:
- Overexpression of Loc646329 downregulated miR-21, PDCD4, and SPRY2, while upregulating PTEN.
- Loc646329, by inhibiting miR-21 and targeting the RAS/MAPK pathway, induced apoptosis and cell cycle arrest in OSCC cells.
- Elevated Loc646329 expression in vivo was associated with smaller tumor size, reduced lymph node metastasis, and improved survival in OSCC patients.
Conclusions:
- Loc646329 functions as a miR-21 sponge, impacting the RAS/MAPK pathway and exhibiting anti-tumor effects in OSCC.
- Targeting the Loc646329-miR-21 regulatory axis presents a promising avenue for novel therapeutic strategies in OSCC.
- Further research into this axis could lead to precision medicine approaches for OSCC treatment.
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