SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing

Abstract

Background and purpose: Serine/arginine-rich splicing factor 1 (SRSF1) is closely related to the development of tumor. Esophageal carcinoma is the common malignant tumor of digestive system. However, the role of SRSF1 in esophageal carcinoma is rarely reported. This study aimed to detect the expression of SRSF1 in esophageal squamous cell carcinoma (ESCC) and its effects on the proliferation, invasion and migration of ESCC cells, and to explore its mechanism. Methods: Forty pairs of ESCC tissues and paracancerous tissues resected at the Fourth Hospital of Hebei Medical University from January 2020 to December 2021 were collected for this study. The expression of SRSF1 in ESCC was detected by immunohistochemistry. The mRNA expression and protein level of SRSF1 in ESCC cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot, respectively. Eca9706 cell with high expression of SRSF1 was selected. The mRNA expression of SRSF1 was reduced by small interfering RNA (siRNA). The proliferation, migration and invasion of Eca9706 cells were detected by cell counting kit-8 (CCK-8), transwell and Matrigel matrix gel assays, respectively. Database was used to analyze the expression of vascular endothelial growth factor A (VEGFA) in ESCC tissues, and the correlation between expressions of SRSF1 and VEGFA was also analyzed. RTFQ-PCR was used to detect the expression levels of VEGFA Iso8a and Iso8b isoform in Eca9706 cells, and the change in VEGFA Iso8a and Iso8b isoform expressions was also detected after knocking down SRSF1. Results: The expression of SRSF1 was significantly higher in ESCC tissues than in normal esophageal tissues (P<0.05). SRSF1 mRNA and protein were highly expressed in Eca9706 cells (both P<0.01). The mRNA expression and protein level of SRSF1 was significantly lower in siRNA-SRSF1 group than in siRNA-NC group (P<0.01). After knocking down SRSF1, the proliferation, migration and invasion abilities of Eca9706 cells were significantly lower compared with siRNA-NC group (all P<0.05). The expression of VEGFA was significantly higher in ESCC tissue than in normal esophageal tissue (P<0.05), and it was positively correlated with the expression of SRSF1 (P<0.01). RTFQ-PCR showed that the level of VEGFA Iso8a expression in Eca9706 cells was significantly higher compared with VEGFA Iso8b (P<0.01). Moreover, the level of VEGFA Iso8a expression was significantly decreased, while the level of VEGFA Iso8b expression increased after knocking down SRSF1 (P<0.01). Conclusion: SRSF1 can promote proliferation, invasion and migration of ESCC Eca9706 cells by possibly regulating VEGFA mRNA splicing.

Keywords

• |esophageal squamous cell carcinoma|serine/arginine-rich splicing factor 1|vascular endothelial growth factor a|cell proliferation|cell migration|cell invasion