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SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

ABSTRACT: Background:Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. Methods:The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. Results:SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. Conclusions:Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

SUBMITTER: Wang JL

PROVIDER: S-EPMC7149931 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

Wang Ji-Lin JL Guo Chun-Rong CR Sun Tian-Tian TT Su Wen-Yu WY Hu Qiang Q Guo Fang-Fang FF Liang Lun-Xi LX Xu Jie J Xiong Hua H Fang Jing-Yuan JY

Cancer cell international 20200410

<h4>Background</h4>Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC.<h4>Methods</h4>The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invas ...[more]

PMID: 32308565

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Project description:BACKGROUND:Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death worldwide. In patients with CRC, metastasis is a crucial problem that leads to treatment failure and is the primary cause of the lethality of colon cancer. Long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in the development, cell growth, apoptosis, and metastasis of CRC. METHOD:We investigated the transcriptome profiles of human lncRNAs in the primary tumor tissues and in the corresponding normal mucosa of two patients with CRC by using a microarray approach. The expression levels of lncRNAs were verified in colon cancer by real-time PCR. Using bioinformatics approach to illustrate putative biological function of Linc00659 in colon cancer. The effects of Linc00659 on cell growth, proliferation, cell cycle and apoptosis were studies by in vitro assays. RESULTS:Our data revealed that compared with adjacent normal tissues, 201 lncRNAs were deregulated (fold change ??4 or ??0.25) in CRC tissues. Among them, the expression levels of Linc00659 were significantly increased in colon cancer, and high expression levels were correlated with poor survival in patients with CRC. Bioinformatics analysis results indicated that Linc00659 was significantly coexpressed with cycle-related genes in CRC. Linc00659 expression knockdown could significantly suppress colon cancer cell growth by impairing cell cycle progression. In addition, our results showed that Linc00659 expression knockdown could accelerate cell apoptosis in colon cancer cells treated with chemotherapy drugs. Meanwhile, our results also demonstrated that silencing of Linc00659 expression leads to cell growth inhibition and induced apoptosis, possibly by suppressing PI3K-AKT signaling in colon cancer. CONCLUSION:Linc00659 is a novel oncogenic lncRNA involved in colon cancer cell growth by modulating the cell cycle. Our findings give an insight into lncRNA regulation and provide an application for colon cancer therapy.

Project description:BackgroundThe mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC).MethodsIn vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients' overall survival (OS) was analyzed by Kaplan-Meier analysis.ResultsEctopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis.ConclusionsTogether, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.

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SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

Publications

SRSF3 functions as an oncogene in colorectal cancer by regulating the expression of ArhGAP30.

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