Promoter hypomethylation up‐regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma

Kong, Ling‐Min; Liao, Cheng-Gong; Chen, Liang; Yang, Hushan; Zhang, Sihe; Zhang, Zheng; Bian, Huijie; Xing, Jinliang; Chen, Zhinan

doi:10.1111/j.1582-4934.2010.01124.x

Cited by 60 publications

(54 citation statements)

References 48 publications

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“…Real-time quantitative RT-PCR was performed as described previously (22). The expression of miR-22 was quantified by TaqMan microRNA assays from Applied Biosystems.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…Western blotting was performed as described previously (22,23). Anti-CD147 mAb was prepared by our laboratory (7).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…The miRNA mimics, antisense miR-22 (As-miR-22), and negative control were synthesized by Genepharma. Cell transfection and dual luciferase reporter assay were performed as described previously (22,23).…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…Our previous studies reported that transcription factor Sp1 could regulate CD147 expression in lung and liver cancers (22,23). Recently, Sp1 was identified as a direct miR-22 target involved in the cancer cell senescence program (20).…”

Section: Introductionmentioning

confidence: 99%

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A Regulatory Loop Involving miR-22, Sp1, and c-Myc Modulates CD147 Expression in Breast Cancer Invasion and Metastasis

et al. 2014

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Breast cancer is the most common cancer in women for which the metastatic process is still poorly understood. CD147 is upregulated in breast cancer and has been associated with tumor progression, but little is known about its regulatory mechanisms. In this study, we demonstrated that CD147 was overexpressed in breast cancer tissues and cell lines, and the high expression correlated with tumor invasion and metastasis. We also found that the transcription factors Sp1 and c-Myc could bind to the CD147 promoter and enhance its expression. The CD147 mRNA has a 748-bp 3 0 -untranslated region (UTR) with many miRNA target sites, suggesting possible regulation by miRNAs. We discovered that miR-22 repressed CD147 expression by directly targeting the CD147 3 0 UTR. We also determined that miR-22 could indirectly participate in CD147 modulation by downregulating Sp1 expression. miR-22 could form an autoregulatory loop with Sp1, which repressed miR-22 transcription by binding to the miR-22 promoter. Together with the c-Myc-mediated inhibition of miR-22 expression, our investigation identified a miR-22/Sp1/c-Myc network that regulates CD147 gene transcription. In addition, miR-22 overexpression suppressed breast cancer cell invasion, metastasis, and proliferation by targeting CD147 in vitro and in vivo. Furthermore, we found that miR-22 was significantly downregulated in breast cancer tissues and that its expression was inversely correlated with the tumor-node-metastasis stage and lymphatic metastasis in patients. Our study provides the first evidence that an miR-22/Sp1/c-Myc network regulates CD147 upregulation in breast cancer and that miR-22 represses breast cancer invasive and metastatic capacities. Cancer Res; 74(14); 3764-78. Ó2014 AACR.

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“…Real-time quantitative RT-PCR was performed as described previously (22). The expression of miR-22 was quantified by TaqMan microRNA assays from Applied Biosystems.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…Western blotting was performed as described previously (22,23). Anti-CD147 mAb was prepared by our laboratory (7).…”

Section: Western Blot Analysismentioning

confidence: 99%

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Regulatory Loop Involving miR-22, Sp1, and c-Myc Modulates CD147 Expression in Breast Cancer Invasion and Metastasis

et al. 2014

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“…11,12 Importantly, the regulation of CD147 in cancer development occurs at the transcriptional and post-transcriptional levels. 13,14 In breast cancer cells, a transcriptional factor Sp1 stimulates its binding activity to the CD147 promoter, and CD147 also promotes Sp1 phosphorylation at T453 and T739. 15 To determine whether CD147 is involved in HBXIP-mediated chemoresistance in ovarian cancer cells, we tested whether HBXIP is able to upregulate CD147.…”

Section: Expression Of Hbxip Is Correlated With Cisplatin Resistance mentioning

confidence: 99%

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer

Zou

Yang

et al. 2017

Exp Biol Med (Maywood)

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We found that hepatitis B X-interacting protein (HBXIP) was able to activate the CD147 promoter through Sp1. In vivo, depletion of HBXIP decreased the tumor volume and weight induced by CP. Taken together, these results indicate that HBXIP promotes cisplatin resistance and regulated CD147 via Sp1 in ovarian cancer cell lines. AbstractOvarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in ovarian cancer cell lines.

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Tiam1 is associated with hepatocellular carcinoma metastasis

Huang

Guan

et al. 2012

Intl Journal of Cancer

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We have previously demonstrated that overexpression of T lymphoma invasion and metastasis 1 (Tiam1) is correlated with poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we tried to further investigate the potential roles of Tiam1 in the progression of HCC in a larger set of samples. By detecting Tiam1 expression in 213 HCC patients, we observed that Tiam1 had a higher probability of being overexpressed in HCC patients with metastasis than those without metastasis (68.3% vs. 52.7%, p = 0.036). In addition, the cell line with high metastatic potential expressed more Tiam1 than did the cell line with low metastatic potential. Overexpression of Tiam1 was suggested to be significantly correlated with HCC metastasis. We stably upregulated Tiam1 expression in MHCC97L as well as knocked down Tiam1 expression in HCCLM6. We also investigated the effects of Tiam1 overexpression and knockdown on HCC cells proliferation, migration and invasion in vitro and on tumorigenicity and metastasis in vivo. Overexpression of Tiam1 increased proliferation, migration and invasion of MHCC97L cells, while knockdown of Tiam1 in HCCLM6 cells resulted in the reverse. In vivo functional studies showed upregulation of Tiam1 expression led to an enhancement of tumorigenicity and metastatic potential in mice. However, knockdown of Tiam1 expression exhibited nearly 2.2-fold retardation in tumor growth and great inhibition on tumor metastases. Our results indicate that Tiam1, as a metastasis-related gene, may contribute to HCC invasion and metastasis, and consequently, it may be a useful biomarker for therapeutic strategy and control in HCC treatment.

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Promoter hypomethylation up‐regulates CD147 expression through increasing Sp1 binding and associates with poor prognosis in human hepatocellular carcinoma

Cited by 60 publications

References 48 publications

A Regulatory Loop Involving miR-22, Sp1, and c-Myc Modulates CD147 Expression in Breast Cancer Invasion and Metastasis

A Regulatory Loop Involving miR-22, Sp1, and c-Myc Modulates CD147 Expression in Breast Cancer Invasion and Metastasis

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer

Tiam1 is associated with hepatocellular carcinoma metastasis

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