SRPK1 is a poor prognostic indicator and a novel potential therapeutic target for human colorectal cancer

Yang, Nan; Xiao, Mingbing; Jiang, Feng; Liu, Zhaoxiu; Ni, Wenkai; Lu, Cuihua; Ni, Runzhou; Chen, Weichang

doi:10.2147/ott.s172541

Cited by 15 publications

(16 citation statements)

References 28 publications

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“…In prostate cancer, SRPK1 overexpression was noted in both cancer and its precursor, PIN (prostatic intraepithelial neoplasia), and was associated with a higher tumor stage [26,37]. Similarly, in colorectal cancer, SRPK1 was overexpressed in both cancer and its precursor, adenoma, compared to the normal colonic tissue [22,31,36,[38][39][40]; its high expression was also linked with higher grade and stage colorectal cancers, presence of lymph node metastases, in addition to shorter overall and recurrence-free survival [31,36,38,39]. In stomach cancer, high SRPK1 was also found compared to the normal stomach histology [31,[41][42][43][44] and was associated with higher grade, stage, larger tumor size, lymph node metastases, and shorter overall survival [41,43,44].…”

Section: Cancer Type (Primary Location)mentioning

confidence: 99%

“…Approach Followed (Testing on Histology Samples/Blood; Data Mining) Level Tested (mRNA; Protein) Clinical Significance Reference Lung data mining; histology samples mRNA; protein ↑SRPK1 was found in NSCLC and was associated with higher tumor stage and shorter survival [29] histology samples mRNA; protein ↑SRPK1 was found in NSCLC [30] data mining mRNA ↑SRPK1 was found in lung adenocarcinoma (a NSCLC histologic type) [31] Breast histology samples mRNA; protein ↑SRPK1 was found in breast cancer and was associated with higher tumor stage and shorter survival [32] histology samples; data mining mRNA; protein ↑SRPK1 was associated with shorter survival in breast cancer and metastatic disease to the lungs and brain [33] data mining mRNA ↑SRPK1 was associated with shorter survival in HER2-negative breast cancer patients treated with chemotherapy [34] histology samples protein ↑SRPK1 was found in breast cancer [35] histology samples protein ↑SRPK1 was found in breast cancer [22] histology samples protein ↑SRPK1 was found in breast cancer and was associated with higher tumor grade [36] Prostate histology samples protein ↑SRPK1 was found in prostate cancer and its precursor (PIN) [26] histology samples protein ↑SRPK1 was found in prostate cancer and was associated with higher stage [37] Colorectal histology samples protein ↑SRPK1 was found in colon cancer and its precursor (adenoma) [22] histology samples protein ↑SRPK1 was found in colon cancer and was associated with higher tumor grade [36] histology samples mRNA; protein ↑SRPK1 was found in colorectal cancer and was associated with higher tumor stage and shorter survival [38] histology samples mRNA; protein ↑SRPK1 was found in colorectal cancer and was associated with higher tumor stage and shorter survival [39] histology samples mRNA ↑SRPK1 was found in colorectal cancer and its precursor (adenoma) [31] histology samples protein ↑SRPK1 and p-AKT were found in colon cancer [40] Stomach data mining mRNA ↑SRPK1 was found in gastric cancer [31] histology samples protein ↑SRPK1 was found in gastric cancer and was associated with higher tumor stage and shorter survival [41] histology samples protein ↑SRPK1 was found in gastric cancer [42] histology samples mRNA; protein ↑SRPK1 was found in gastric cancer and was associated with higher tumor stage and shorter survival [43] Liver histology samples mRNA; protein ↑SRPK1 was associated with higher stage and shorter survival; SRPK1 expression was inversely correlated with miR-1296 expression…”

Section: Cancer Type (Primary Location)mentioning

confidence: 99%

“…The SRPK1/SRSF1 axis regulates VEGF-A alternative splicing (proangiogenic vs. antiangiogenic VEGF isoforms) [26] Colorectal ↑SRPK1 was found in colorectal cancer cell lines ↓SRPK1 induced apoptosis and sensitivity to chemotherapy in vitro SRPK1 interacts with the AKT and MAPK pathways and modulates MAP2K2 alternative splicing [36] ↑SRPK1 was found in colorectal cancer cell lines and induced proliferation in vitro ↓SRPK1 suppressed growth, angiogenesis, migration and induced apoptosis in vitro [38] ↑SRPK1 was found in colorectal cancer cell lines ↓SRPK1 suppressed proliferation, migration and invasion in vitro SRPK1 interacts with the miR-216b [39] Stomach ↑SRPK1 was found in gastric cancer cell lines and promoted proliferation and invasion in vitro ↓SRPK1 suppressed proliferation and invasion in vitro SRPK1 interacts with the AKT and ERK pathways [41] ↑SRPK1 promoted proliferation in vitro and in vivo ↓SRPK1 suppressed proliferation both in vitro and in vivo SRPK1 interacts with the small nucleolar RNA-mediated pathways [42] ↑SRPK1 was found in gastric cancer cell lines and promoted proliferation, migration, and invasion in vitro ↓SRPK1 suppressed proliferation, migration, and invasion in vitro SRPK1 interacts with miR-126 [43] ↑SRPK1 was found in gastric cancer cell lines ↓SRPK1 abolished the IGF-1-mediated expression of EMT markers, induced cell cycle arrest and suppressed migration and invasion in vitro…”

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

confidence: 99%

“…Second, like prostate cancer, it also suppressed angiogenesis through a switch in VEGF alternative splicing resulting in higher expression of the VEGF165b isoform [62]. Third, it enhanced apoptosis and resistance to chemotherapy [36,38,61]. Of interest, deregulated alternative splicing was also found to play a role in colorectal carcinogenesis.…”

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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Section: Cancer Type (Primary Location)mentioning

confidence: 99%

Section: Cancer Type (Primary Location)mentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…To date, there are commercially available SRPK inhibitors including SRPIN340 and SRPKIN‐1 for inhibiting both SRPK1/2, whereas SPHINX31 was designed to be specific only to SRPK1 . Small interfering RNA (siRNA) is another tool to suppress SRPK protein expression . However, both inhibitors and siRNA can reduce SRPK function transiently.…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9‐mediated double knockout of SRPK1 and SRPK2 in a nasopharyngeal carcinoma cell line

et al. 2019

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Background: Serine-arginine protein kinase (SRPK) is a regulator of alternative splicing events via phosphorylation of splicing factor proteins. Oncogenic roles of SRPK1 and SRPK2 have been reported in various types of cancer. To date, only SRPK1/2 specific inhibitors and small interfering RNA (siRNA) have been used for halting their function momentarily; however, there is no attempt to generate SRPK1/2 stable knockout cancer cells as a tool to investigate their roles in tumorigenesis.Aim: Our objective is therefore to establish a nasopharyngeal carcinoma (NPC) cell line with stable SRPK1 or SRPK2 knockout and SRPK1/2 double knockout as a model to investigate their potential roles in NPC.Methods and Results: CNE1 was selected as a representative of NPC cell lines to create single and double knockout of SRPK1/2 proteins. SRPK1/2 KO plasmid with cas9, green fluorescent protein (GFP), and gRNA expression was cotransfected with SRPK1/2 homology-directed repair (HDR) plasmid containing puromycin resistance, red fluorescent protein (RFP), and 5 0 and 3 0 arm sequence for homologous recombination to CNE1 cells. The transfected CNE1 cells with GFP and RFP expression were sorted through fluorescence-activated cell sorting for further treatment with puromycin containing medium. This step generated stable single knockout of SRPK1 and SRPK2. The SRPK2 knockout NPC cells were used as a precursor for double knockout generation via transfection with Cre plasmid for excision of inserted material to generate puromycin-sensitive SRPK2 knockout clone. The puromycin-sensitive SRPK2 knockout cells were transfected with SRPK1 KO/HDR plasmid and treated with puromycin-containing medium. The puromycin-resistant cells of SRPK1/2 stable double knockout were expanded, and the corresponding protein expression was confirmed by western immunoblotting analysis.Conclusion: Single and double knockout of SRPK1/2 were established using clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated 9 (Cas9) system in an NPC cell line as a model for investigation of their splicing mechanism in NPC. K E Y W O R D Salternative splicing, SRPK1, SRPK2, CRISPR/Cas9, nasopharyngeal carcinoma

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SRPKs: a promising therapeutic target in cancer

Tufail

2023

Clin Exp Med

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SRPK1 is a poor prognostic indicator and a novel potential therapeutic target for human colorectal cancer

Cited by 15 publications

References 28 publications

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

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

CRISPR/Cas9‐mediated double knockout of SRPK1 and SRPK2 in a nasopharyngeal carcinoma cell line

SRPKs: a promising therapeutic target in cancer

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