Inclusion of hnRNP L Alternative Exon 7 Is Associated with Good Prognosis and Inhibited by Oncogene SRSF3 in Head and Neck Squamous Cell Carcinoma

Figure 5

(a) The model of autoregulation of SRSF3 expression is regulated by hnRNP L. SRSF3 has an alternative exon 4, which has an in-frame stop codon. The longer isoform with exon 4 is degraded via NMD or encodes a truncated SRSF3 protein. The shorter isoform without exon 4 can encode full-length functional SRSF3 protein. SRSF3 promotes the inclusion of its own exon 4 to maintain relatively stable levels of SRSF3 in cells. HnRNP L inhibits the inclusion of exon 4. (b-c) The correlation between the ratios of SRSF3 exon 4 inclusion versus exclusion and hnRNP L exon 7 inclusion versus exclusion in the TCGA head and neck cancer dataset (520 cases) and breast cancer dataset (1093 cases). (d) Kaplan-Meier curves of overall survival for patients with both low hnRNP L exon 7 and SRSF3 exon 4 inclusion (41 cases), low hnRNP L exon 7 inclusion only (43 cases), or both not low hnRNP L exon 7 and SRSF3 exon 4 inclusion (none, 297 cases). Low inclusion of hnRNP L exon 7 was defined as less than mean-0.8SD (standard deviation). Low inclusion of SRSF3 exon 4 was defined as less than mean-0.66SD. (e) The model of SRSF3 and hnRNP L mutually inhibiting their autoregulation and promoting carcinogenesis.

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