Loc646329 sponges miR-21 to reduce RAS/MAP kinase signaling pathway in oral squamous cell carcinoma (OSCC).

Autor: Adereh A; Yasuj University of Medical Science, Yasuj, Iran., Amini P; Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Fateh A; Shahid Sadoughi University of Medical Sciences, Yazd, Iran., Faghihkhorasani F; Department of Cardiology, Internal Medicine, The first affiliated Hospital of Xi'an Jiaotong University, Xian, Shaanxi Province, 710061, China., Khdakarim N; Assistant Professor of Hematology & Oncology, Department of Internal Medicine, School of Medicine, Hazrat-E Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran., Marashi SM; Tehran University of Medical Sciences, Tehran, Iran., Ahadi S; School of Medicine, Jondishapour University of Medical Sciences, Ahvaz, Iran., Nayebzadeh P; University of Georgia, Tbilisi, Georgia., Khanmirzaei A; Faculty of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. amirk.mirzaei@gmail.com.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Dec 14. Date of Electronic Publication: 2024 Dec 14.
DOI: 10.1007/s00210-024-03671-x
Abstrakt: 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.
Competing Interests: Declarations. Ethics approval: This study was approved by the Ethical/Scientific Committee of Shahroud University of Medical Sciences (IR.SHMU.AEC.1401.002). Our ethics committee/IRB permits a maximal tumor size/burden of 5 cm in diameter. We confirm that the maximal tumor size/burden was not exceeded in our study. All tumors included were within the permitted size limit. In this study, for working with vertebrate animals, all the ethical protocols based on the guidelines of the Basel Declaration have been followed. Informed consent: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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