Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of matched esophageal squamous cell carcinoma (ESCC) and normal tissue samples as well as two cell lines were analyzed. AS events with significant differences were identified between ESCC and matched normal tissues, which were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events were found. Of these, 6,019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues, as well in the two cell lines were found. Four pathways and 20 biological processes related to pro-metastasis cell junction and migration were significantly enriched for the differentially spliced genes. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Differentially spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1 are shown with a sashimi plot. These results suggest that cell junction- and migration-related biological processes are influenced by AS abnormalities, and aberrant splicing events can be affected by splicing factor expression changes. The involved splicing factor SF3B4 was found to be a survival-related gene in ESCC and is presumed to regulate AS in multiple cancers. In summary, we identified significant differentially expressed AS events which may be related to the development of ESCC.

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Posted 13 Jan, 2021
On 26 Jan, 2021
Received 12 Jan, 2021
On 05 Jan, 2021
Invitations sent on 04 Jan, 2021
On 02 Jan, 2021
On 02 Jan, 2021
On 02 Jan, 2021
Received 03 Nov, 2020
On 03 Nov, 2020
On 11 Oct, 2020
Received 14 Aug, 2020
On 05 Aug, 2020
On 03 Aug, 2020
Invitations sent on 01 Aug, 2020
On 22 Jul, 2020
On 21 Jul, 2020
On 30 Jun, 2020
On 27 Jun, 2020
Posted 13 Jan, 2021
On 26 Jan, 2021
Received 12 Jan, 2021
On 05 Jan, 2021
Invitations sent on 04 Jan, 2021
On 02 Jan, 2021
On 02 Jan, 2021
On 02 Jan, 2021
Received 03 Nov, 2020
On 03 Nov, 2020
On 11 Oct, 2020
Received 14 Aug, 2020
On 05 Aug, 2020
On 03 Aug, 2020
Invitations sent on 01 Aug, 2020
On 22 Jul, 2020
On 21 Jul, 2020
On 30 Jun, 2020
On 27 Jun, 2020
Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of matched esophageal squamous cell carcinoma (ESCC) and normal tissue samples as well as two cell lines were analyzed. AS events with significant differences were identified between ESCC and matched normal tissues, which were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events were found. Of these, 6,019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues, as well in the two cell lines were found. Four pathways and 20 biological processes related to pro-metastasis cell junction and migration were significantly enriched for the differentially spliced genes. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Differentially spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1 are shown with a sashimi plot. These results suggest that cell junction- and migration-related biological processes are influenced by AS abnormalities, and aberrant splicing events can be affected by splicing factor expression changes. The involved splicing factor SF3B4 was found to be a survival-related gene in ESCC and is presumed to regulate AS in multiple cancers. In summary, we identified significant differentially expressed AS events which may be related to the development of ESCC.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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