Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-κB signaling

Li, J; Wu, Heshui; Li, W; Yin, Liangyu; Guo, Shixiang; Xu, Xiang; Ouyang, Yueping; Zhao, Zhiping; Liu, S; Tian, Y; Tian, Zhiqiang; Ju, Jingfang; Ni, Bing; Wang, H

doi:10.1038/onc.2016.90

Cited by 146 publications

(119 citation statements)

References 48 publications

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“…The SPHK1-expressing lentivirus was constructed by inserting the SPHK1 open reading frame into the pLenti6.3 vector (Invitrogen), as previously described [21]. …”

Section: Methodsmentioning

confidence: 99%

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma

Wang

et al. 2016

Oncotarget

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Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo.Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.

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“…The SPHK1-expressing lentivirus was constructed by inserting the SPHK1 open reading frame into the pLenti6.3 vector (Invitrogen), as previously described [21]. …”

Section: Methodsmentioning

confidence: 99%

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma

Wang

et al. 2016

Oncotarget

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“…Immunohistochemistry was performed as previously described [28]. Ki-67-positive cells were defined as those with brown staining in the nucleus, and expression of Ki-67 was evaluated based on the percentage of positive cells among 1000 tumor cells.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

“…Cell transfection DCLK1 siRNA (GGGAGUGAGAACAAUCUACtt) and negative control siRNA were transfected using RNAiMAX (Invitrogen, Camarillo, CA, USA) at a final concentration of 100 nM, as previously described [28].…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

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Doublecortin-Like Kinase 1 (DCLK1) Regulates B Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (Bmi-1) and is Associated with Metastasis and Prognosis in Pancreatic Cancer

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression. Methods: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay. Results: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly. Conclusion: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.

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“…miRNAs can modulate a plethora of protein-coding genes that are involved in the development, progression and metastatic spread of PDAC cells [22,82]. As a result, the potential for miRNAs to be used as prognostic markers in PDAC has been extensively studied.…”

Section: Ncrnas As Prognostic Biomarkersmentioning

confidence: 99%

Noncoding Rnas as Novel Biomarkers in Pancreatic Cancer: what do we Know?

et al. 2016

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Pancreatic cancer is an aggressive cancer of the digestive system, which is becoming a serious health problem worldwide. Overall survival for patients with pancreatic cancer is poor, mainly due to a lack of biomarkers to enable early diagnosis and a lack of prognostic markers that can inform decision-making, facilitating personalized treatment and an optimal clinical outcome. ncRNAs play an important role in pancreatic carcinogenesis. Here we review the literature on the role of ncRNAs as biomarkers in pancreatic cancer. We focus on the significance of ncRNAs as markers for early diagnosis, as prognostic biomarkers able to inform clinical management and as targets for novel therapeutics for patients with pancreatic cancer.

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Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-κB signaling

Cited by 146 publications

References 48 publications

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma

Doublecortin-Like Kinase 1 (DCLK1) Regulates B Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (Bmi-1) and is Associated with Metastasis and Prognosis in Pancreatic Cancer

Noncoding Rnas as Novel Biomarkers in Pancreatic Cancer: what do we Know?

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