Down‐regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis in Xuanwei Female Lung Cancer Patients

Zhou, Yunyun; Wang, Xicai; Huang, Yunchao; Chen, Yan; Yao, Qian; Jin, Congguo; Huang, Yang H.; Liu, Xin; Li, Guangjian

doi:10.1002/jcb.25055

Cited by 32 publications

(20 citation statements)

References 29 publications

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“…The down-regulation of CXCL8 and SOX4 expression in the knockdown cells for GOLGB1 or SF3B3 were further validated by qRT-PCR (Figure 6E), supporting that CXCL8 and SOX4 are the downstream targets of GOLGB1 and SF3B3 . Indeed, previous studies have established well that the CXCL8 (IL-8) and SOX4 can promote cancer development and progression [25, 26]. In addition, we could observe positive correlations of the expression levels of GOLGB1 or SF3B3 with the expression levels of CXCL8 and SOX4 in the liver cancer data of TCGA, implying the potential connection between them (Supplementary Figure 5).…”

Section: Resultssupporting

confidence: 64%

Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype

et al. 2016

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Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells. Transcriptome analysis also revealed that the recurrent HCCs reprogram their transcriptomes to acquire aggressive phenotypes. Network analysis revealed CXCL8 (IL-8) and SOX4 as common downstream targets of the mutants. In conclusion, we suggest that the mutations of GOLGB1 and SF3B3 are potential key drivers for the acquisition of an aggressive phenotype in recurrent HCC.

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Section: Resultssupporting

confidence: 64%

Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype

et al. 2016

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“…We particularly focused on SOX4 because it has previously been shown to regulate the levels of p53, the master regulator of apoptosis (Hur et al 2010;Zhou et al 2015). There have been conflicting reports on the effect of SOX4 on p53 levels.…”

Section: Discussionmentioning

confidence: 99%

P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer

Sharma

Nagpal

Ghosh

et al. 2017

RNA

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miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that was a direct target of miR-191-5p. overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment.

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“…Studies have also reported that overexpression of Sox4 was closely associated with tumor progression and metastasis (31,32). Sox4 maybe a crucial oncogene affecting tumor progression and metastasis in HCC and lung cancer (10,33). Overexpression of Sox4 has also been detected in other types of solid tumors including prostate, breast, bladder and lung cancer (7,34,35).…”

Section: Discussionmentioning

confidence: 98%

“…Overexpression of Sox4 has also been detected in other types of solid tumors including prostate, breast, bladder and lung cancer (7,34,35). Downregulation of the expression of Sox4 inhibited cell proliferation, metastasis and induced apoptosis in lung cancer cells (33).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑132‑3p regulates cell proliferation, apoptosis, migration and invasion of liver cancer by targeting Sox4

Huang

Xiang

et al. 2020

Oncol Lett

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The present study investigated whether microRNA (miR)-132-3p targeted transcription factor SOX-4 (Sox4) for the inhibition of proliferation, migration, invasion and promotion of apoptosis in liver cancer (LC) cells. The expression of miR132-3p and Sox4 mRNA was evaluated by quantitative PCR and protein expression was determined by western blot analysis. Cell proliferation, apoptosis, migration, and invasion were assessed at different time points by the MTT assay, flow cytometry analysis, wound healing assay and Transwell migration assay, respectively. Bioinformatics prediction and luciferase assays were performed to validate and confirm Sox4as a potential target of miR-132p. There was a reduced expression of miR-132-3p in HepG2 and Huh7 cell lines compared with HccLM3 cells. Overexpression of miR-132-3p resulted in significant inhibition of proliferation and induction of apoptosis in LC cells. Moreover, migration and invasion of HepG2 cells were suppressed by over expressing miR-132-3p. However, downregulation of miR-132-3p in Hep-G2 cells promoted cell growth, invasion and migration and inhibited apoptosis. Bioinformatics analysis predicted Sox4 as a potential target of miR-132-3p, which was further confirmed by the luciferase reporter assay. In addition, an inverse association was observed between miR-132-3p and Sox4 expression. miR-132-3p may regulate the proliferation, apoptosis, migration and invasion of HepG2 cells by targeting Sox4.

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Down‐regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis in Xuanwei Female Lung Cancer Patients

Cited by 32 publications

References 29 publications

Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype

Mutations acquired by hepatocellular carcinoma recurrence give rise to an aggressive phenotype

P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer

MicroRNA‑132‑3p regulates cell proliferation, apoptosis, migration and invasion of liver cancer by targeting Sox4

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