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Cancer Chemotherapy and Pharmacology

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12.09.2019 | Original Article

Downregulation of SRSF3 by antisense oligonucleotides sensitizes oral squamous cell carcinoma and breast cancer cells to paclitaxel treatment

verfasst von: Yanan Sun, Lingyan Yan, Jihua Guo, Jun Shao, Rong Jia

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2019

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Abstract

Purpose

Paclitaxel (PTX) is widely used in the chemotherapy of many cancers, including breast cancer and oral squamous cell carcinoma (OSCC). However, many patients respond poorly to PTX treatment. The SRSF3 oncogene and several splicing factors play important roles in OSCC tumorigenesis. This study aimed to understand the function of splicing factors in PTX treatment and improve the therapeutic effects of PTX treatment.

Methods

Splicing factors regulated by PTX treatment were screened in CAL 27 cell by reverse transcription polymerase chain reaction. The function of SRSF3 in PTX treatment was analyzed by gain-of-function or loss-of-function assay in OSCC cell lines CAL 27 and SCC-9 and breast cancer cell line MCF-7. Alternative splicing of SRSF3 exon 4 in cancer tissues or cells was analyzed by RT-PCR and online program TSVdb. SRSF3-specific antisense oligonucleotide (ASO) SR-3 was used to downregulate SRSF3 expression and enhance the effect of PTX treatment.

Results

PTX treatment decreased SRSF3 expression, and SRSF3 overexpression rescued the growth inhibition caused by PTX in both OSCC and breast cancer cells. Moreover, we found that PTX treatment could repress SRSF3 exon 4 (containing an in-frame stop codon) exclusion and then decrease the SRSF3 protein expression. Increased exclusion of SRSF3 exon 4 is correlated with poor survival in OSCC and breast cancer patients. SR-3 downregulated SRSF3 protein expression and significantly increased the sensitivity of cancer cells to PTX treatment.

Conclusions

SRSF3 downregulation by ASO sensitizes cancer cells to PTX treatment.

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Titel: Downregulation of SRSF3 by antisense oligonucleotides sensitizes oral squamous cell carcinoma and breast cancer cells to paclitaxel treatment
verfasst von: Yanan Sun
Lingyan Yan
Jihua Guo
Jun Shao
Rong Jia
Publikationsdatum: 12.09.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03945-9

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Downregulation of SRSF3 by antisense oligonucleotides sensitizes oral squamous cell carcinoma and breast cancer cells to paclitaxel treatment

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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