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PDK4 gene can be used as a biomarker for the treatment of prostate cancer

2021-04-28
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In the development of anti-cancer drugs, many researchers have been paying attention to finding special genetic markers to help identify those patients with prostate cancer that are more prone to worsening and those who can successfully use drug treatment or respond well, trying to find a relationship with prostate cancer. New genetic biomarkers related to the process. Understanding and identifying biomarkers is an important step in cancer research and treatment. Biomarker detection technology can enrich people’s understanding of biomarkers, obtain a large amount of data and experience, and solve many biological or medical problems. Biomarkers have become a key element in the research and development of international anti-tumor drugs.

The relationship between STAT3 protein and prostate cancer

Signal transducer and activator of transcription 3 (STAT3) is a member of the family of signal transducers and activators of transcription. In many tumor cell lines and human tumor tissue specimens, there is continuously activated STAT3 protein, and the activated STAT3 protein is important for tumor cells. Formation, growth, and inhibition of apoptosis all play a very important regulatory role. For example, STAT3 is abnormally activated in liver cancer and other chronic inflammation-related tumors. As a key signaling molecule in the inflammatory microenvironment of liver cancer, STAT3 not only participates in the “inflammation to cancer transformation” in the process of liver cancer, but also promotes the proliferation, invasion and metastasis of cancer cells in the progress of liver cancer through a variety of ways. It is a potential liver cancer treatment target . The expression of STAT3 protein is also closely related to the occurrence and development of prostate cancer.

The types of expression vectors include prokaryotic cell expression vectors and mammalian expression vectors. The cloning of human STAT3 gene and constructing it on mammalian expression vectors is very important for the functional research of STAT3 protein. siRNA is a small interfering RNA fragment. It has been reported that a 21bp small RNA fragment can specifically inhibit gene expression in mammalian cells without activating the antiviral response of the host cell, thus causing RNAi in mammals. Research boom.

Regarding the relationship between STAT3 protein and prostate cancer, some researchers constructed a small interfering RNA (siRNA) expression vector of STAT3 and tested its inhibitory effect on STAT3 expression and prostate cancer cell line PC-3 cell proliferation. The results of the study found that the STAT3 siRNA expression vector constructed with pSilencerTM2.1 U6 vector can effectively inhibit the expression of STAT3 and the proliferation of prostate cancer cells [1]. Medicilon researchers have established a mature mammalian protein expression system and purification service platform to provide expression and purification services for mammalian protein expression systems.

Some researchers have also explored the expression and significance of STAT3 in prostate cancer tissues. The researchers used immunohistochemical methods to detect the expression of STAT3 in 40 cases of prostate cancer and 12 cases of normal prostate tissue. The results of the study found that STAT3 is highly expressed in most prostate cancer tissues, which is significantly higher than that in normal tissues, suggesting that the expression of STAT3 may be closely related to the occurrence and development of prostate cancer [2].

In 2015, a team led by Lukas Kenner, a molecular pathologist at the Medical University of Vienna, unexpectedly discovered that the STAT3 protein plays a role in suppressing prostate cancer in a mouse model. They showed that, compared with patients with high levels, patients with low levels of STAT3 in cancer cells had significantly worse disease progression.

A report recently published in the journal Molecular Systems Biology stated that Monika Oberhuber, a doctoral candidate from the Kenner team of the Department of Pathology, Vienna Medical University, and the Austrian Biotechnology Research Medical Center , COMET Competence Center (funded by the Austrian Research Promotion Agency (FFG)) jointly conducted a study. Studies have found that pyruvate dehydrogenase kinase 4 (PDK4) is directly related to the STAT3 protein, and its gene expression can be used as an independent prognostic marker for prostate cancer, which can predict prostate cancer recurrence and diagnose risk factors. The biomarkers in the body are similar to the warning lights of a car. When they send a signal, they may need to be repaired. In our body, the biomarkers can indicate that there is something wrong with the body, or that we are about to get sick. Sign.

The relationship between pyruvate dehydrogenase kinase 4 (PDK4) and STAT3 protein

The research team analyzed many large patient data sets and compared patients with high and low STAT3 expression in their tissues. This leads to the identification of correlations between the expression characteristics of different gene clusters. Researchers found that patients with low STAT3 had an active metabolism. Metabolism (especially cellular respiration) is much more active in prostate tumors than in healthy prostate tissue. This provides additional growth energy for the tumor. Patients with low STAT3 showed higher cellular respiration and more active tumors, in which many new proteins were formed.

  Researcher Oberhaber also used paraffin-embedded tissue sections to study the relationship between low STAT3 and active metabolism. A laser microscope is used to separate the tumor tissue from the healthy tissue, and then use mass spectrometry to analyze. The results show that there is a direct correlation between STAT3 and PDK4, which slows down cellular respiration. Patients showing low STAT3 also have low PDK4, which can prove that PDK4 is directly regulated by STAT3. This means that the level of PDK4 can predict the course of the disease well. In other words, the prognosis of prostate cancer patients with low PDK4 is worse than that of prostate cancer patients with high PDK4. The PDK4 gene also plays an important role in the occurrence of other tumors and diseases (such as diabetes). A follow-up study of PDK4 is now planned to study its potential application in the treatment of prostate cancer.

Finding a biomarker that can accurately detect prostate cancer at an early stage and determine tumor aggressiveness is crucial for the development of anti-tumor drugs. If biomarkers can indeed predict the development of prostate cancer cells, they can provide ideas for the development of new drugs for the treatment of prostate cancer, and this new type of biomarkers can also help distinguish fast-developing and slow-developing tumor tissues. The development of drugs for the treatment of prostate cancer provides a wealth of information.

[1] Construction of STAT3 specific small interfering RNA expression vector and its inhibition of STAT3 expression [J].

[2] The expression and significance of STAT3 protein in prostate cancer tissues [J].

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