The crucial role of SRPK1 in TGF-β-induced proliferation and apoptosis in the esophageal squamous cell carcinomas

Ren, Guohua; Sheng, Lijun; Li, Haibo; Sun, Yanlai; An, Yu; Li, Yan

doi:10.1007/s12032-015-0654-3

Cited by 24 publications

(18 citation statements)

References 17 publications

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“…SRPK1, a highly conserved protein in precursor mRNA translation and splicing, chromatin reconstruction, is dysregulated in different cancers [26, 35]. Moreover, SRPK1 play a critical role in EMT process of human glioblastoma [36].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

et al. 2017

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BackgroundIncreasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown.MethodsThe levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay.ResultsWe found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296.ConclusionsUnderexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0675-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

et al. 2017

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“…Aberrant SRPK1 expression in either direction can induce constitutive Akt activation and provide a mechanistic basis for previous observations that SRPK1 can be downregulated in some cancer types but upregulated in others (25). Ren et al (26) revealed that SRPK1 mediated TGF-Î²-induced proliferation and apoptosis by regulating AKT and JNK in ESCC. Thus, the TGF-Î²-SRPK1 pathway may be a useful target to affect the progression of ESCC.…”

Section: Discussionmentioning

confidence: 60%

SRPK1‑siRNA suppresses K562 cell growth and induces apoptosis via the PARP‑caspase3 pathway

Wang

Wen

et al. 2017

Mol Med Report

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Serine-arginine protein kinase 1 (SRPK1) has been used as an important signal mediator, and is associated with cancer development. However, studies have yet to determine whether SRPK1 suppresses leukemia cell growth and induces apoptosis. Studies have also yet to reveal the underlying mechanisms. In the present study, the effects of downregulating SRPK1 gene expression on chronic myeloid leukemia cell lines (K562 cells) were investigated through RNA interference (RNAi) and the proliferation inhibition and apoptosis induction of SRPK1 in K562 cells were analyzed. K562 cells were transfected with two different concentrations of siRNA, and the transfection efficiency was detected via flow cytometry. The expression of SRPK1 was detected via reverse transcription‑quantitative polymerase chain reaction. K562 cell proliferation and apoptosis were analyzed using MTT and flow cytometry respectively. The roles of caspase‑3, poly (ADP‑ribose) polymerase (PARP), p53 and B-cell lymphoma (Bcl)‑2/Bcl‑2 associated X, apoptosis regulator (Bax) proteins in the apoptosis of human K562 cells were further examined through western blot analysis. The SRPK1 expression was lower in the K562 cells transfected with SRPK1‑siRNA compared with untransfected cells. The inhibition rate in the transfected groups was increased compared with the untransfected groups. Compared with control groups, the number of apoptotic cells in the SRPK1‑silenced groups increased. The number of early apoptotic cells also increased. The cleaved caspase‑3, cleaved PARP and p53 expression levels were significantly increased in the RNAi groups compared with control groups. Conversely, the Bcl‑2/Bax rate was significantly lower. In conclusion, the knockdown of the SRPK1 gene by RNAi inhibited the proliferation of K562 cells and induced their apoptosis. Apoptosis was induced by the activation of the PARP‑caspase3 pathway.

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“…Liver cancer was also characterized by SRPK1 overexpression, while the latter was correlated with higher stage, larger tumor size, and shorter survival [45][46][47]. In esophageal cancer, high expression of SRPK1 was associated with higher grade, stage, the capacity to metastasize, and shorter overall survival at both univariate and multivariate levels [48].…”

Section: Cancer Type (Primary Location)mentioning

confidence: 98%

“…The SRPK1-induced PI3K/AKT pathway interacts with miR-1296 [45] ↑SRPK1 was found in hepatocellular cancer cell lines [46] ↑SRPK1 was found in hepatocellular cancer cell lines and promoted proliferation ↓SRPK1 suppressed proliferation in vitro and growth in vivo and in vitro SRPK1 interacts with the PI3K/AKT pathway [47] Esophagus ↑SRPK1 was found in esophageal cancer cell lines and promoted proliferation ↓SRPK1 suppressed proliferation, migration, and invasion and enhanced apoptosis in vitro also suppressed tumor growth in vivo SRPK1 interacts with the TGF-β pathways [48] Pancreas ↑SRPK1 was found in pancreatic cancer cell lines ↓SRPK1 suppressed proliferation and enhanced apoptosis and sensitivity to chemotherapy in vitro SRPK1 interacts with SR proteins and regulates apoptosis [22] SRPK1 interacts with the AKT and MAPK pathways [36] Blood (Leukemia) ↓SRPK1 suppressed proliferation in vitro and tumor growth in vivo, while it enhanced cell cycle arrest, apoptosis and prolonged the survival of animal models in MLL-rearranged AML; ↓SRPK1 switched BRD4 splicing, favoring the production of its long isoform SRPK1 modulates the alternative splicing of BRD4, MYB, and MED24 [65] ↑SRPK1 was found in various myeloid and lymphoid leukemia cell lines ↓SRPK1 was cytotoxic and enhanced apoptosis in vitro SRPK1 interacts with the SR proteins and modulates the expression and splicing of MAP2Ks, VEGF, and FAS [66] ↓SRPK1 suppressed proliferation while it enhanced autophagy and apoptosis in a synergistic fashion with chemotherapy in vitro SRPK1 interacts with SR proteins and modulates the expression of MAP2Ks and VEGF and the splicing of RON [67] ↓SRPK1 suppressed proliferation and enhanced apoptosis in vitro in CML SRPK1 interacts with the PARP-caspase-3 pathway [68] Kidney ↑SRPK1 was found in renal cancer cell lines ↓SRPK1 suppressed proliferation, migration, and invasion in vitro, also tumor growth in vivo SRPK1 interacts with PI3K/AKT pathway [50] Brain (Glioma) ↑SRPK1 was found in glioma cell lines ↓SRPK1 suppressed proliferation, migration, and invasion of glioma cells in vitro while it induced resistance to chemotherapy [51] ↓SRPK1 suppressed tumor growth and apoptosis in vivo, also angiogenesis in vitro and in vivo…”

Section: ↓Srpk1 Suppressed Migration and Invasion In Vitromentioning

confidence: 99%

“…In liver cancer, it suppressed proliferation, migration, and invasion [45,47]. In esophageal cancer, it suppressed proliferation, migration, invasion and enhanced apoptosis [48], while in pancreatic cancer it suppressed proliferation and also enhanced apoptosis and sensitivity to chemotherapy [22]. In kidney cancer, SRPK1 low expression suppressed proliferation, migration, and invasion [50].…”

Section: Srpk1-mediated Mechanism(s)/ Pathway(s) Involved Referencementioning

confidence: 99%

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Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Nikas

Themistocleous

Paschou

et al. 2019

Cells

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Cancer, a heterogeneous disease composed of tumor cells and microenvironment, is driven by deregulated processes such as increased proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis. Alternative splicing, a mechanism led by splicing factors, is implicated in carcinogenesis by affecting any of the processes above. Accumulating evidence suggests that serine-arginine protein kinase 1 (SRPK1), an enzyme that phosphorylates splicing factors rich in serine/arginine domains, has a prognostic and potential predictive role in various cancers. Its upregulation is correlated with higher tumor staging, grading, and shorter survival. SRPK1 is also highly expressed in the premalignant changes of some cancers, showing a potential role in the early steps of carcinogenesis. Of interest, its downregulation in preclinical models has mostly been tumor-suppressive and affected diverse processes heterogeneously, depending on the oncogenic context. In addition, targeting SRPK1 has enhanced sensitivity to platinum-based chemotherapy in some cancers. Lastly, its aberrant function has been noted not only in cancer cells but also in the endothelial cells of the microenvironment. Although the aforementioned evidence seems promising, more studies are needed to reinforce the use of SRPK1 inhibitors in clinical trials. major area of research in the field of intratumor heterogeneity, while their presence is associated with cancer recurrence, metastasis, and resistance to chemotherapy [7].Cancer prognosis depends on multiple factors that affect survival. Tumor staging, traditionally performed with the TNM system, is the most important prognostic factor. It refers to the size of the tumor (T), also the extent of its spread to the regional lymph nodes (N) or distant metastatic sites (M) [8,9]. Grading refers to the histologic picture of the tumor, more specifically, how closely it looks compared to the normal tissue it derives from (differentiation) [10,11]. Both the presence of distant metastases (e.g., in lungs, brain, liver, bones) and poor differentiation are associated with a dismal prognosis [9,11]. The molecular subtype of specific cancers is also critical for cancer survival. For instance, breast cancer has diverse intrinsic subtypes-luminal A and B, human epidermal growth factor receptor 2-enriched (HER2-enriched), and basal-like-that directly impact prognosis [12][13][14]. Luminal breast cancers are most commonly hormone-positive, overexpressing estrogen receptors (ER), and are associated with a better prognosis than HER2-enriched or basal-like breast cancers (BLBCs) [12][13][14][15]. BLBCs, which most commonly present with a triple-negative phenotype, have been linked with the worst prognosis and highest metastatic potential of all breast cancer molecular subtypes [13,16,17].Alternative splicing is the process that removes introns and adds exons in various combinations resulting in multiple mRNA products hence protein transcripts. As a result, it maintains the protein diversity and cellular homeostasis [18]. The...

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The crucial role of SRPK1 in TGF-β-induced proliferation and apoptosis in the esophageal squamous cell carcinomas

Cited by 24 publications

References 17 publications

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

SRPK1‑siRNA suppresses K562 cell growth and induces apoptosis via the PARP‑caspase3 pathway

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

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