Identification of RNA-splicing factor Lsm12 as a novel tumor-associated gene and a potent biomarker in Oral Squamous Cell Carcinoma (OSCC)

作者：Dong Yan, Liyan Xue, Yan Zhang, Caiyun Liu, Yanguang Zhang, Na Jiang, Xiaoyan Ma, Fangyu Chen, Lingxia Li, Liyuan Yu, Xuefeng Liu, Shujuan Shao, Shufang Guan, Jian Zhang, Qingchun Xiao, Hui Li, Ailing Dong, Lijie Huang, Chenyang Shi, Yan Wang, M.W. Fu, Ning Lv, Qimin Zhan · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2022 · DOI：10.1186/s13046-022-02355-9 · 被引用次数：24 · 研究领域：RNA Research and Splicing、Cancer-related molecular mechanisms research、RNA and protein synthesis mechanisms

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 ...