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Function and use of PHF14

A 1.PHF14, purpose technology, applied in the field of chemical biology research in life sciences, can solve problems such as limited proportion of patients

Active Publication Date: 2018-07-20
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some molecularly targeted drugs have been developed for cancer treatment, but the proportion of patients who can respond well to these drugs is still very limited, and further development of tumor molecularly targeted drugs is imminent

Method used

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  • Function and use of PHF14
  • Function and use of PHF14
  • Function and use of PHF14

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0167] Embodiment 1, experimental material and experimental method

[0168] 1. Experimental materials

[0169] 1.1 Strain: Escherichia coli DH5α: The strain is used for the construction and amplification of the plasmid.

[0170] 1.2 Mammalian cell lines

[0171] (1) Hfl-1: human embryonic lung fibroblasts, derived from normal male fetal lungs, with fibroblast-like morphology, normal diploid structure, adherent culture and passage, used as a control group for normal lung cancer cells.

[0172] (2) Human lung cancer cell lines: A549, H2126, CRL-5803, CRL-5807, CRL-5810, CRL-5844, CRL-5872, CRL-5883, CRL5889, CRL-5908, CRL5928.

[0173] (3) HCT-116: Human colon cancer cells, derived from adult male colon cancer, are epithelioid cells in morphology, adherent culture and passage, and strong tumorigenicity. In this cell line, the expression of PHF14 is lost (Ivanov et al. , 2007), so this cell line was selected as a natural PHF14-deficient cell model for functional experiments in...

Embodiment 2

[0244] Example 2, Detection of the expression level of PHF14 in tumor samples

[0245] In order to detect the relationship between PHF14 and cancer, we collected five types of clinical tumor samples and their corresponding paracancerous samples (kidney cancer, gastric cancer, colon cancer, liver cancer and non-small cell lung cancer). We found that the expression of PHF14 in lung cancer was significantly up-regulated in terms of gene copy number, mRNA and protein level ( Figure 1A -D). The results of WB and immunohistochemistry indicated that more than 80% of lung cancer tissue samples showed a high expression level of PHF14 protein compared with adjacent tissues. qPCR also showed that 71% of patients had increased PHF14 mRNA levels. Analysis of the correlation between the expression level of PHF14 and clinical data (Table 1) shows that its high expression (score>12) is associated with adenocarcinoma, and it is significantly high in early lung cancer (TNM I, or tumor diamete...

Embodiment 3

[0248] Example 3, down-regulating the expression of PHF14 can significantly inhibit the proliferation of lung cancer cells

[0249] Based on the findings at the clinical sample level of cancer patients, we selected human lung cancer cell lines for functional experiments. The expression of PHF14 in two different human lung cancer cells, A549 and CRL-5810, was knocked down by RNAi, and the effect of down-regulation of PHF14 expression on the proliferation and tumorigenesis of lung cancer was observed. MTT results showed that PHF14 knockdown significantly inhibited the growth and proliferation of A549 and CRL-5810 lung cancer cells ( Figure 2A , 2B); BrdU incorporation experiments (to detect the speed of DNA synthesis) also proved that reducing the expression of PHF14 can inhibit the DNA synthesis of cells and thus inhibit the proliferation of cells. In addition, we constructed an RNAi resistant PHF14 expression plasmid to rescue the slow cell growth after PHF14 knockdown

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Abstract

The invention belongs to the field of chemical biology researches in the life sciences, and specifically relates to a function and a use of PHF14. A result of extensive and advanced researches show that the PHF14 can be used as a lung cancer treatment target individually or together with KIF4A for the first time, and the expression of the PHF14 and / or KIF4A can be inhibited to significantly inhibit the growth and proliferation of lung cancer cells, inhibit the deterioration of the lung cancer cells and inhibit the tumor forming ability of the lung cancer cells. Strong scientific evidences areprovided for the pathogenesis of lung cancer and the clinical treatment of lung cancer at the clinical patient sample level, the cell function level and the molecular level.

Description

technical field [0001] The invention belongs to the field of chemical biology research in life sciences, and specifically relates to the function and application of PHF14. Background technique [0002] PHD finger protein is a kind of PHD finger protein that widely exists in eukaryotes and plays an important role in gene transcription regulation and disease occurrence. In recent studies, the PHD finger protein has been classified as a "reader" protein that can recognize histone methylation modifications (Lan et al., 2007; Org et al., 2008; Shi et al., 2006; Wysocka et al., 2006), this family of proteins plays an important role in regulating cellular epigenetic modifications. Different PHD finger proteins can specifically recognize different "histone marks" and regulate the transcriptional expression of genes by regulating their intrinsic activity or by regulating the activity of their interacting proteins (Baker et al., 2008). More and more studies have shown that when poin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K45/06A61P35/00C12Q1/6886
CPCA61K45/00A61K45/06C12Q1/6886C12Q2600/158
Inventor 陈正军张喆
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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