Open Access

ARTICLE

Exosomal microRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

YI LI¹, TIANYI WANG¹, HAORAN DING¹, SHIYONG ZHUANG¹, XIAOBO DAI¹, BING YAN^1,2,*
1 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
2 Frontier Innovation Center for Dental Medicine Plus, Chengdu, 610041, China
* Corresponding Author: BING YAN. Email:

Oncology Research https://doi.org/10.32604/or.2024.048191

Received 29 November 2023; Accepted 15 April 2024; Published online 20 May 2024

Abstract

Background: Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation. Methods: Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes. Results: let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells. Conclusion: Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.

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Keywords

Oral cancer; Exosomal microRNA; let-7c-5p; Tumorigenesis biomarkers; Gene expression profiling; TAGLN

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