Analysis of differential splicing gene by regulation of splicing regulatory protein KHSRP in lung adenocarcinoma

Background and purpose: Alternative splicing plays a crucial role in the functions and regulation of complex proteins such as cell proliferation, growth, apoptosis and differentiation, and can cause the occurrence and development of various diseases, including cancer. Currently, the functions and molecular mechanisms of most alternative splicing factors are not clear. The purpose of this study was to explore the differential splicing target genes of KH-type splicing regulatory protein (KHSRP) in lung adenocarcinoma and their correlation with prognosis and immune cell function. Methods: Screening downstream differential splicing target genes of KHSRP was carried out through high-throughput variable splicing sequencing. We analyzed the expressions of KHSRP downstream differential splicing target genes in lung adenocarcinoma through cancer databases Tumor IMmune Estimation Resource (TIMER) and the University of Alabama at Birmingham cancer data analysis portal (ULCAN). We also analyzed the correlation between the expression of differential splicing target genes downstream of KHSRP and prognosis through Kaplan database. The correlation between downstream differential splicing target genes of KHSRP and immune cell function was analyzed through the TIMER immune module. Results: NUMB endocytic adaptor protein (NUMB), adducin 3 (ADD3) and LIM and calponin homology domains 1 (LIMCH1) were key downstream variable splicing target genes of KHSRP. NUMB, ADD3 and LIMCH1 were all expressed at low level in lung adenocarcinoma tumor tissue. Low expressions of NUMB, ADD3 and LIMCH1 in lung cancer leaded to poor prognosis. NUMB, ADD3 and LIMCH1 were positively correlated with immune cell function. Conclusion: In lung adenocarcinoma, NUMB, ADD3 and LIMCH1 are differential splicing target genes of KHSRP, their low expression levels indicate poor prognosis, and they are positively correlated with immune cell function.