Background: Oral squamous cell carcinoma (OSCC) is one of the common cancers worldwide. The lack of specific biomarkers and therapeutic targets leads to delayed diagnosis and hence the poor prognosis of OSCC patients. Thus, it is urgent to identify effective biomarkers and therapeutic targets for OSCC.
Methods: We established the golden hamster carcinogenic model of OSCC induced by 7,12-dimethylbenz(a) anthrancene (DMBA) and used mRNA microarrays to detect the differentially expressed genes (DEGs). DEGs were validated in OSCC clinical tissue microarrays using immunohistochemistry method. Whole transcriptome sequencing was performed to obtain an overview of biological functions of Lsm12. PCR assay and sequencing were employed to investigate the alternative splicing of genes regulated by Lsm12. Cell proliferation, colony formation, Transwell migration and invasion assay and in vivo tumor formation assay were performed to investigate the roles of Lsm12 and two transcript variants of USO1 in OSCC cells.
Results: Lsm12 was identified to be significantly up-regulated in the animal model of OSCC tumorigenesis, which was validated in the clinical OSCC samples. In the paired normal tissues, Lsm12 staining was negative (91%, 92/101) or weak, while in OSCC tissues, positive rate is 100% and strong staining spread over the whole tissues in 93 (93/101, 92%) cases. Lsm12 overexpression significantly promoted OSCC cell growth, colony formation, migration and invasion abilities, while Lsm12 knockdown showed the opposite trends on these phenotypes and obviously inhibited the tumor formation in vivo. Furthermore, Lsm12 overexpression caused the inclusion of USO1 exon 15 and Lsm12 knockdown induced exon 15 skipping. Exon 15-retained USO1 significantly promoted the malignant phenotypes of OSCC cells when compared with the exon 15-deleted USO1.
Conclusions: We identified Lsm12, a novel tumorigenesis-related gene, as an important regulator involved in OSCC tumorigenesis. Lsm12 is a novel RNA-splicing related gene and can regulate the alternative splicing of USO1 exon 15 which was associated closely with OSCC carcinogenesis. Our findings thus provide that Lsm12 might be a potent biomarker and potential therapeutic target for OSCC.
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http://dx.doi.org/10.1186/s13046-022-02355-9 | DOI Listing |
Epigenomics
December 2024
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Technical Institute of Physics and Chemistry, University of Chinese Academy of Sciences, Beijing 100190, China; Hangzhou CASbios Medical Co., Hangzhou 310000, China. Electronic address:
Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in the oral and maxillofacial region. Traditional treatments for OSCC, including surgery, radiotherapy, and chemotherapy, often lead to severe adverse effects. Therefore, the development of safe and effective novel cancer therapies is crucial for achieving synergistic cancer treatment, significantly enhancing patient survival and quality of life.
View Article and Find Full Text PDFIET Syst Biol
December 2024
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Oral squamous cell carcinoma (OSCC) is a common head and neck malignant tumour with high incidence and poor prognosis. Arsenic trioxide (ATO) has therapeutic effects on solid tumours. Microwave ablation (MWA) has unique advantages in the treatment of solid tumours.
View Article and Find Full Text PDFJ Dent (Shiraz)
December 2024
Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Statement Of The Problem: Squamous cell carcinomas (SCCs) and premalignant disorders such as leukoplakia are common oral cavity lesions. Although these lesions are epithelial in nature, they are also associated with juxta-epithelial chronic inflammation. Mast cells play a significant role in inflammation initiation and propagation.
View Article and Find Full Text PDFOtolaryngol Head Neck Surg
December 2024
Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Objectives: We investigate if sublingual space invasion (SLI) determined on magnetic resonance imaging confers differences in clinicopathological manifestations and treatment outcomes of oral tongue squamous cell carcinoma (OTSCC).
Study Design: Retrospective cohort study.
Setting: Tertiary Academic Medical Center.
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