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SRSF3-mediated Ki67 exon 7 alternative splicing regulates Head and Neck Squamous Cell Carcinoma progression via AKR1C2

ABSTRACT: SRSF3-mediated Ki67 exon 7 alternative splicing regulates Head and Neck Squamous Cell Carcinoma progression via AKR1C2

PROVIDER: PRJNA878796 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21503304_1.fastq.gz	Fastqsanger.gz
	SRR21503304_2.fastq.gz	Fastqsanger.gz
	SRR21503305_1.fastq.gz	Fastqsanger.gz
	SRR21503305_2.fastq.gz	Fastqsanger.gz
	SRR21503306_1.fastq.gz	Fastqsanger.gz

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SRSF3-mediated Ki67 exon 7 alternative splicing regulates Head and Neck Squamous Cell Carcinoma progression via AKR1C2

Project description:The roles of Ki67 exon 7 have rarely been reported.SCC-9 cells were transfected with siE7 and siNC on day 0 and day 2, total RNA was extracted using TRIzol Reagent (Invitrogen, USA) and then used for mRNA sequencing (Wuhan Seqhealth Co., Ltd. China).

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SRSF3-Mediated Ki67 Exon 7-Inclusion Promotes Head and Neck Squamous Cell Carcinoma Progression via Repressing AKR1C2.

Project description:Ki67 is a well-known proliferation marker with a large size of around 350 kDa, but its biological function remains largely unknown. The roles of Ki67 in tumor prognosis are still controversial. Ki67 has two isoforms generated by alternative splicing of exon 7. The roles and regulatory mechanisms of Ki67 isoforms in tumor progression are not clear. In the present study, we surprisingly find that the increased inclusion of Ki67 exon 7, not total Ki67 expression level, was significantly associated with poor prognosis in multiple cancer types, including head and neck squamous cell carcinoma (HNSCC). Importantly, the Ki67 exon 7-included isoform is required for HNSCC cell proliferation, cell cycle progression, cell migration, and tumorigenesis. Unexpectedly, Ki67 exon 7-included isoform is positively associated with intracellular reactive oxygen species (ROS) level. Mechanically, splicing factor SRSF3 could promote exon 7 inclusion via its two exonic splicing enhancers. RNA-seq revealed that aldo-keto reductase AKR1C2 is a novel tumor-suppressive gene targeted by Ki67 exon 7-included isoform in HNSCC cells. Our study illuminates that the inclusion of Ki67 exon 7 has important prognostic value in cancers and is essential for tumorigenesis. Our study also suggested a new SRSF3/Ki67/AKR1C2 regulatory axis during HNSCC tumor progression.

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