Lentivirus-mediated short hairpin RNA targeting the APRIL gene suppresses the growth of pancreatic cancer cells in vitro and in vivo

Wang, Feng; Chen, Lin; Mao, Zhen-biao; Shao, Jian-guo; Tan, Chang; Huang, Weida

doi:10.3892/or.20.1.135

Cited by 17 publications

(15 citation statements)

References 26 publications

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“…However, downstream signaling cascades activated by APRIL that may be involved in tumor formation have yet to be characterized. We recently confirmed that APRIL is overexpressed in digestive system carcinomas, specifically in the colon and pancreas [13], [14], [15]. APRIL is more highly expressed in tumors than in normal colon, and APRIL-knockdown inhibited the migration and invasion of colorectal cancer cells in vitro [16].…”

Section: Introductionmentioning

confidence: 60%

APRIL Induces Tumorigenesis and Metastasis of Colorectal Cancer Cells via Activation of the PI3K/Akt Pathway

Wang

Ding

et al. 2013

PLoS ONE

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A proliferation-inducing ligand (APRIL) is highly expressed in colorectal cancer (CRC) tissues and cell lines. However, the biological functions and precise signals elicited by APRIL in CRC have not been fully understood. Here, we used small interfering RNA to selectively deplete APRIL and to determine its tumorigenic effects in a CRC cell line SW480 both in vitro and in vivo. Knockdown of APRIL in SW480 cells was associated with modulation of cell proliferation as well as reduction of cell migration and invasion in vitro. Moreover APRIL-knockdown SW480 cells displayed markedly inhibited tumor growth and decreased metastasis to the liver in immunodeficient mice upon subcutaneous injection. Importantly, we observed that downregulation of APRIL in SW480 cells resulted in greatly decreased activity of phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, we observed that recombinant human APRIL mediated activation of the PI3K/Akt pathway in CRC cells resulting in induced expression of important cell cycle proteins and matrix metalloproteinases in a PI3K/Akt dependent manner. This was concurrent with marked cell growth viability as well as increased cell migration and invasion. Together, these compelling data suggest that APRIL-induced tumorigenesis and metastasis of CRC cells may be accomplished through activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of APRIL and may provide clues for identifying novel therapeutic and preventive molecular markers for CRC.

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Section: Introductionmentioning

confidence: 60%

APRIL Induces Tumorigenesis and Metastasis of Colorectal Cancer Cells via Activation of the PI3K/Akt Pathway

Wang

Ding

et al. 2013

PLoS ONE

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“…In the case of TNFSF13, their role in cancer is not clear but other family members APRIL (a proliferation inducing ligand) and BAFF (B cell activating factor) play a role in chronic lymphocytic leukemia (CLL) [35] by increasing the survival of leukemic cells through blocking the apoptosis. The shRNA mediated blocking of APRIL The genes are grouped according to their cellular functions resulted in reduced growth of pancreatic tumour cells [46]. From our studies we observe an increase in 11E6 and a decrease in 18E6 compared to the mock.…”

Section: Transcription Regulationmentioning

confidence: 61%

Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

Ganguly

2015

VirusDis.

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Human papilloma virus is the causative agent for cervical cancer with 99 % of cervical cancer cases containing HPV. The high risk HPV-16, 18 and 31 are the major causative agents. The low risk HPV-6, 11 have been reported to cause penile, laryngeal, bronchogenic and oesophageal cancer. Since E6 oncoprotein is frequently over expressed in cancers, we did gene expression studies to compare between the E6 genes of high-risk (HPV18) or low-risk (HPV11)stably transfected in epithelial cell line EPC-2 or mock transfected with the basic vector pCDNA3.1. Microarray studies showed a total of 697 genes showing differential expression between the samples. Genes involved in several key cellular processes such as cell adhesion, angiogenesis, transcription regulation, cell cycle regulation and cell division showed altered expression between the samples. Gene Ontology mapping of 44 genes according cellular pathways revealed 13 pathways namely angiogenesis, alzhemier's, Wnt, p53, interleukin, TGF-b, cadherin, integrin, PI3-kinase, catennin, insulin, chemokine and G protein signalling pathways. The microarray results were confirmed by quantitative real-time PCR for some representative genes like IFI27, CTNNA1, OSMR, CYP1B1, TNFSF13, LAMA2 and COL5A3. Analysis of differentially expressed genes by high-risk and lowrisk HPV E6 proteins might help in identification of potential biomarkers for diagnosis, progression and therapy of oesophageal cancer. The understanding of mechanisms of activation of these genes as well as the function of gene products will give a further insight into their roles in oesophageal cancer.

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“…However, studies have confirmed that it is overexpressed in many tumor tissues and many tumor cell lines, especially in the digestive system carcinomas, such as colon carcinoma, pancreatic cancer, gastric cancer, hepatoma and esophageal carcinoma, which suggests that APRIL has an important role in the occurrence and development of these tumors. [15][16][17][18][19] Our previous experiments have further confirmed that APRIL is overexpressed in CRC tumors, yet, it is not expressed or has a weak expression in normal colon mucosa tissues. Moreover, several CRC cell lines have been screened and it has been found that SW480 cell line is highly expressed in the APRIL gene.…”

Section: Introductionmentioning

confidence: 79%

Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells

et al. 2011

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MicroRNAs (miRNAs) regulate mammalian gene expression by targeting mRNAs and have key roles in several cellular processes, including differentiation, development, apoptosis and cancer pathomechanisms. Our previous studies have confirmed that a proliferation-inducing ligand (APRIL) gene is overexpressed in colorectal cancer (CRC) tumors and SW480 cells. To study the potential mechanisms of APRIL gene in the occurrence and development of the CRC, herein, we investigated whether APRILknockdown had the inhibitory effect on the growth of SW480 cells and had the simultaneous expression changes of miRNAs and mRNAs by microarrays. Our results suggest that siRNA-APRIL can effectively inhibit the growth of SW480 cells in vitro and in vivo and several miRNAs via specific pathways might be involved in regulating the phenotype of loss-of-function in APRIL-knockdown SW480 cells. Thus, our study highlights the possible mechanisms of miRNA-target regulating the function of APRIL gene in CRC cells, moreover, siRNA-APRIL holds great promise as a novel gene therapy approach for APRIL-positive CRC treatment.

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Lentivirus-mediated short hairpin RNA targeting the APRIL gene suppresses the growth of pancreatic cancer cells in vitro and in vivo

Cited by 17 publications

References 26 publications

APRIL Induces Tumorigenesis and Metastasis of Colorectal Cancer Cells via Activation of the PI3K/Akt Pathway

APRIL Induces Tumorigenesis and Metastasis of Colorectal Cancer Cells via Activation of the PI3K/Akt Pathway

Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells

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