Dataset Information

Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells.

ABSTRACT: Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1. MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation. Following MALAT1 knockdown, overexpression of SRPK1 was sufficient to restore SRSF1 phosphorylation and AKAP-9 expression to a level that promoted cell proliferation, invasion and migration in vitro. Conversely, SRPK1 knockdown after overexpression of MALAT1 in SW480 cells diminished SRSF1 phosphorylation and AKAP-9 expression and suppressed cell proliferation, invasion and migration in vitro. These findings suggest MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in CRC cells. These results reveal a novel molecular mechanism by which MALAT1 regulates AKAP-9 expression in CRC cells.

SUBMITTER: Hu ZY

PROVIDER: S-EPMC4905507 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells.

Hu Zhi-Yan ZY Wang Xiao-Yan XY Guo Wen-Bin WB Xie Lin-Ying LY Huang Yu-Qi YQ Liu Yan-Ping YP Xiao Li-Wei LW Li Sheng-Nan SN Zhu Hui-Fang HF Li Zu-Guo ZG Kan Heping H

Oncotarget 20160301 10

Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1. MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation. Following MALAT1 knockdown, ove ...[more]

PMID: 26887056

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Project description:BackgroundAs a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C-C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis.MethodsBioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down and RNA binding protein immunoprecipitation experiments were performed to determine the MALAT1-microRNA-202-3p (miR-203-3p) interaction and miR-202-3p-SRSF1 interaction followed by the analysis of their effect on the mTOR pathway.ResultsCCL21 was identified as a key GC immune gene. Overexpressed CCL21, MALAT1, and SRSF1 along with poorly expressed miR-202-3p were identified in the GC cells. CCL21 induced the MALAT1 expression in a time- and dose-dependent manner. Functionally, MALAT1 targeted miR-202-3p but upregulated SRSF1 and activated mTOR. Crucially, evidence was obtained indicating that CCL21 promoted both the malignant phenotypes and EMT of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo by increasing the MALAT1-induced upregulation of SRSF1.ConclusionsTaken together, the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.

Dataset Information

Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells.

Publications

Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells.

Similar Datasets

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