Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial tumor in the oral cavity. Emerging evidence has demonstrated the important function roles of long noncoding RNAs (lncRNAs) in human cancers. LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) functions as an oncogene in multiple carcinomas, whereas its function in OSCC has not been investigated yet. The aim of our study is to investigate the possible regulatory mechanism of PANDAR in OSCC. First of all, PANDAR was highly expressed in OSCC cells and loss-of-function assays mediated by CRISPR-dCas9 observed that PANDAR silencing restrained cell proliferation and promoted cell apoptosis. Then we found and confirmed the interaction between PANDAR and serine and arginine rich splicing factor 7 (SRSF7). Subsequently, serine/threonine-protein kinase pim-1 (PIM1) was proved to be regulated by PANDAR in SRSF7-dependant way. Rescue experiments validated that PANDAR modulated the proliferation and apoptosis in OSCC through PIM1. In conclusion, PANDAR bound with SRSF7 to increase PIM1 expression, hence promoting the development of OSCC. These data shed new lights into the seeking for effective diagnostic biomarkers and therapeutic targets for OSCC patients.
Highlights
Oral squamous cell carcinoma (OSCC) is a well-known cancer that accounts for more than 90% of all types of oral cancers (Bagan et al, 2010)
To explore whether long noncoding RNAs (lncRNAs) PANDAR affects the biological activities of OSCC cells, we initially examined the expression level of PANDAR in OSCC cells (SAS, Cal27, SCC9, SCC15, and SCC4) and normal oral keratinocytes (NOKs)
Numerous researches have demonstrated the crucial roles of long noncoding RNAs in human tumors, including OSCC
Summary
Oral squamous cell carcinoma (OSCC) is a well-known cancer that accounts for more than 90% of all types of oral cancers (Bagan et al, 2010). Due to efforts made on cancer therapy, such as radiotherapy, chemotherapy, and molecular target therapy, the 5-year relative survival more than doubled in the last 26 years for OSCC (Sutton et al, 2003; Jerjes et al, 2010; van Putten et al, 2018). The pathogenesis and molecular mechanism of OSCC have not been clear, and further research is needed. SP1-induced lncRNA CASC11 promotes the tumorigenesis of glioma by targeting FOXK1 through sponging miR-498 (Jin et al, 2019). APF lncRNA affects autophagy and myocardial infarction by sponging miR-188-3p (Wang et al, 2015). DLX6-AS1 promotes pancreatic cancer development by regulating miR-497-5p/FZD4/FZD6/
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