Application of SLC7A11 gene in hepatocellular carcinoma interventional embolization post operation

A technology of SLC7A11, 1.SLC7A11, applied in the field of molecular biology, can solve problems such as unclear understanding, and achieve the effect of rescuing tumor suppression

Pending Publication Date: 2021-11-23
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, our knowledge of the precise mechanisms of ferroptosis ...

Method used

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  • Application of SLC7A11 gene in hepatocellular carcinoma interventional embolization post operation
  • Application of SLC7A11 gene in hepatocellular carcinoma interventional embolization post operation
  • Application of SLC7A11 gene in hepatocellular carcinoma interventional embolization post operation

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Experimental program
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Effect test

Embodiment 1

[0090] Hypoxia inhibits METTL14-induced ferroptosis in vitro in a HIF-1α-dependent manner:

[0091] To determine the role of METTL14 and RNA m6A modification under hypoxic conditions, METTL14 was first detected in the presence of 1% O 2 Expression in Huh7 and HCCLM3 cell lines (hypoxia conditions, Hypoxia). The results showed that hypoxia effectively decreased METTL14 and increased HIF-1α expression in two HCC cell lines compared with the control group (normoxia, Normoxia), as Figure 1A shown. Then, shRNA was used to knock down HIF-1α, and the results showed that inhibition of HIF-1α strongly prevented hypoxia-induced downregulation of METTL14, as shown in Figure 1B As shown, this suggests that hypoxia-triggered METTL14 repression is HIF-1α-dependent. Ferroptosis is a regulated form of cell death that has been shown to be tumor suppressive and useful in cancer therapy. ROS and MDA are recognized indicators of ferroptosis. To investigate the effect of hypoxia on ferroptos...

Embodiment 2

[0093] METTL14 negatively regulates the expression of SLC7A11 in HCC:

[0094] To explore the underlying mechanism by which METTL14 regulates ferroptosis, the expression patterns of METTL14 and SLC7A11, a core member of the system xc- that mediates ferroptosis, were analyzed using multiple databases. First, the expression pattern of METTL14 in HCC patients versus healthy patients was analyzed in The Cancer Genome Atlas (TCGA) and Oncomine databases. Compared with normal liver, the expression level of METTL14 in HCC patients was down-regulated by 1.052 times (p=7.32×10 -9 ), 1.059 times (p=4.86×10 -4 ); on the other hand, the overall survival of HCC patients with lower expression of METTL14 was shorter than that of patients with higher expression of METTL14, such as Figure 2A shown. In addition, the expression of SLC7A11 in HCC patients and healthy subjects was further analyzed in the Oncomine databases "Wurmbach Liver", "Roessler Liver" and "Roessler Liver 2". Compared wi...

Embodiment 3

[0098] METTL14 triggers m6A methylation at the 5'UTR of SLC7A11 mRNA in HCC:

[0099] To verify the specific relationship between SLC7A11 and METTL14, RNA Base v2.0 (http: / / www.sysu.edu.cn) was first checked and found several potential m6A sites within the 5'UTR of SLC7A11 mRNA, like Figure 3A As shown, this suggests that SLC7A11 may be regulated by METTL14 in an m6A-dependent manner. It has been demonstrated that the R298P mutation greatly reduces METTL14 methylation activity. Therefore, stable METTL14-R298P expressing Huh7 and HCCLM3 cell lines were established, as Figure 3B shown. To determine whether the m6A modification of SLC7A11 is mediated by METTL14, the total m6A levels in the negative control group and the stable METTL14 overexpression group as well as the METTL14-R298P group were first detected by m6A dot blot. As expected, m6A levels were significantly increased with METTL14 overexpression but decreased in two HCC cell lines with the R298P mutation, as Fi...

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Abstract

The invention discloses an application of an SLC7A11 gene in a hepatocellular carcinoma interventional embolization post operation. On the basis of molecular biology experiments, it is verified that SLC7A11 is a key member of a ferroptosis signal channel, and related small-molecule inhibitors are found and designed for SLC7A11 and related signal molecule channels to intervene in proliferation and apoptosis of liver cancer cells; and animal model experiments prove that the proliferation and migration of HCC cells can be inhibited by knocking down the SLC7A11 through a small-molecule inhibitor (shRNA of the SLC7A11), the tumor inhibition effect of METTL14 induced under the HCC hypoxia condition can be remarkably saved through overexpression of the SLC7A11, and a new molecular target is provided for inhibiting recurrence and metastasis of HCC after liver cancer interventional embolization clinically.

Description

technical field [0001] The invention relates to the application of SLC7A11 gene in hepatocellular carcinoma after interventional embolization, and belongs to the field of molecular biology technology. Background technique [0002] Hepatocellular carcinoma (HCC), the most common primary liver cancer, is typically characterized by rapid proliferation and early metastasis. Both the Barcelona Clinic Liver Cancer (BCLC) Criteria and the Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) recommend the treatment of HCC at different stages. However, more treatments are still needed clinically, because the disease is usually diagnosed in the middle and advanced stages, and the five-year survival rate of HCC patients is still not ideal. [0003] Interventional therapy has been widely used in patients with unresectable HCC. However, the hypoxic state caused by interventional embolism may promote the proliferation and metastasis of HCC cells, and...

Claims

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Application Information

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IPC IPC(8): A61K31/7088A61P35/00A61P35/04C12N15/113
CPCA61K31/7088A61P35/00A61P35/04C12N15/113C12N2310/14
Inventor 刘嵘束敏峰韩红范卓阳高洋张巍杨国威王建华颜志平
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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