Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

Jung Chun Lin, Ching Yu Lin, Woan Yuh Tarn, Fang Yu Li

研究成果: 雜誌貢獻文章

35 引文 (Scopus)

摘要

Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1Stranscripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1Stranscripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.
原文英語
頁(從 - 到)1621-1631
頁數11
期刊RNA
20
發行號10
DOIs
出版狀態已發佈 - 十月 1 2014

指紋

Arginine Kinase
RNA-Binding Proteins
Serine
Apoptosis
Breast Neoplasms
Carcinogenesis
Proteins
RNA Splicing
Gene Silencing
Introns
Exons
Neoplasms
Up-Regulation
RNA-Binding Motifs

ASJC Scopus subject areas

  • Molecular Biology
  • Medicine(all)

引用此文

Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. / Lin, Jung Chun; Lin, Ching Yu; Tarn, Woan Yuh; Li, Fang Yu.

於: RNA, 卷 20, 編號 10, 01.10.2014, p. 1621-1631.

研究成果: 雜誌貢獻文章

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abstract = "Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1Stranscripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1Stranscripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.",
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AU - Lin, Jung Chun

AU - Lin, Ching Yu

AU - Tarn, Woan Yuh

AU - Li, Fang Yu

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1Stranscripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1Stranscripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.

AB - Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1Stranscripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1Stranscripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.

KW - Alternative splicing

KW - Breast cancer

KW - MCL-1

KW - RNA binding motif protein 4

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