SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer

Kim, Hak-Ryul; Lee, Gyeong-Ok; Choi, Keum-Ha; Kim, Dong Kwan; Ryu, Ji Won; Hwang, Ki-Eun; Na, Kook-Joo; Choi, Chan; Kuh, Ja Hong; Chung, Myoung Ja; Lee, Mikyoung; So, Hong-Seob; Yoon, Kwon‐Ha; Park, Min-Cheol; Na, Kyong-Suk; Kim, Young-Suk; Park, Do‐Sim

doi:10.1016/j.lungcan.2016.05.018

Cited by 45 publications

(29 citation statements)

References 12 publications

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“…SRSF5 expression is increased, associated with lymph node metastasis, and involved in the production of the anti-apoptotic form of Mcl-1 in breast cancers 41 . SRSF5 also stimulates proliferation of lung cancer cells 42 . In HCC, however, SRSF5 is downregulated 43 .…”

Section: Discussionmentioning

confidence: 99%

TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3

Fujita

Higashitsuji

Liu

et al. 2017

Sci Rep

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Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood. By screening the serine/arginine-rich splicing factors (SRSFs), we report that the transcript and protein levels of SRSF5 were increased in mammalian cells cultured at 32 °C. Expression of SRSF5 as well as CIRP and RBM3 were also induced by DNA damage, hypoxia, cycloheximide and hypotonicity. Immunohistochemical studies demonstrated that SRSF5 was constitutively expressed in male germ cells and the level was decreased in human testicular germ cell tumors. SRSF5 facilitated production of p19 H-RAS, and increased sensitivity to doxorubicin in human U-2 OS cells. Induction of CIPs was dependent on transient receptor potential vanilloid 4 (TRPV4) channel protein, but seemed independent of its ion channel activity. These findings indicate a previously unappreciated role for the TRP protein in linking environmental stress to splicing.

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Section: Discussionmentioning

confidence: 99%

TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3

Fujita

Higashitsuji

Liu

et al. 2017

Sci Rep

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“…We also uncovered that hnRNPK activates the expression of the splicing regulator SRSF1. The serine/arginine (SR) protein family is an important class of splicing regulators and its members, including SRSF1, SRSF3, and SRSF6, have shown multiple proto-oncogenic properties and aberrant expressions in various cancer cells [25][26][27]. A recent study has indicated that SRSF1 could promote the splicing of CD44V6 (V6 exon-containing isoform) splicing in breast cancer cells [18].…”

Section: Open Accessmentioning

confidence: 99%

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Peng

Liu

et al. 2019

Cancer Cell Int

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Background: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood.Methods: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated.Results: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (− 65 to − 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). Conclusion:These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

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“…A similar switch might also occur during cellular stress, oncogenic transformation, or viral infection, which could explain the contradictory observation that SRSF5 promotes the translation of viral transcripts in infected HeLa cells (Swanson et al, 2010). So far, SRSF5 has been poorly studied, despite being an emerging marker for several cancer types (Kim et al, 2016). The cell type-and state-specific differences in nucleocytoplasmic shuttling of SR protein family members observed herein underline the importance of the cellular context for the function of these and other multifunctional RBPs.…”

Section: Discussionmentioning

confidence: 99%

Cellular differentiation state modulates the mRNA export activity of SR proteins

Botti

McNicoll

Steiner

et al. 2017

Journal of Cell Biology

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SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer

Cited by 45 publications

References 12 publications

TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3

TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Cellular differentiation state modulates the mRNA export activity of SR proteins

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