lincRNA-ROR通过miR-145-ZEB2调控HERC5介导的p53蛋白ISG化修饰在肝纤维

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2023年12月14日发(作者：)

lincRNA-ROR通过miR-145-ZEB2调控HERC5介导的p53蛋白ISG化修饰在肝纤维化中的作用及机制研究

摘要：

肝纤维化是慢性肝病的常见并发症，失控的细胞增殖和过度沉积的胶原是其主要特征。长链非编码RNA ROR（lincRNA-ROR）在多种疾病中扮演着重要角色。本研究对lincRNA-ROR在肝纤维化中的作用机制进行了深入的探究。实验结果表明，lincRNA-ROR的表达水平在肝纤维化病变组织中显著升高。通过建立肝纤维化模型，我们发现lincRNA-ROR通过miR-145/ZEB2调控HERC5介导的p53蛋白ISG化修饰在肝纤维化中发挥了重要作用。这为肝纤维化的治疗提供了新的分子靶点和治疗策略。

关键词：肝纤维化、lincRNA-ROR、miR-145/ZEB2、HERC5、p53蛋白ISG化修饰

Abstract:

Hepatic fibrosis is a common complication of chronic

liver disease, and uncontrolled cell proliferation and

excessive deposition of collagen are its main

characteristics. Long non-coding RNA ROR (lincRNA-ROR)

plays an important role in various diseases. In this study, we explored the mechanism of lincRNA-ROR in

liver fibrosis. The results showed that the expression

level of lincRNA-ROR was significantly increased in

liver fibrosis tissues. By establishing a liver

fibrosis model, we found that lincRNA-ROR mediated by

miR-145/ZEB2 regulates HERC5-mediated p53 protein ISG

modification plays an important role in liver fibrosis.

This provides a new molecular target and treatment

strategy for the treatment of liver fibrosis.

Keywords: liver fibrosis, lincRNA-ROR, miR-145/ZEB2,

HERC5, p53 protein ISG modification

Liver fibrosis is a complex disease that can result in

the development of cirrhosis and liver cancer. It is

characterized by the accumulation of excess collagen

and other extracellular matrix components in the liver.

This process is associated with the activation of

hepatic stellate cells (HSCs) and the secretion of

pro-inflammatory cytokines and growth factors. Despite

extensive research, the molecular mechanisms driving

liver fibrosis remain poorly understood.

In recent years, long noncoding RNAs (lncRNAs) have

emerged as important regulators of gene expression in

many biological processes, including fibrosis.

LincRNA-ROR is a well-known lncRNA that has been implicated in cancer, stem cell pluripotency, and

neuronal differentiation. However, its role in liver

fibrosis is not yet clear.

In this study, we investigated the expression and

function of lincRNA-ROR in liver fibrosis. We found

that the expression level of lincRNA-ROR was

significantly increased in liver fibrosis tissues

compared to healthy controls. We then established a

liver fibrosis model in mice and found that lincRNA-ROR played a critical role in the development and

progression of liver fibrosis.

Further analysis revealed that lincRNA-ROR regulated a

key pathway involved in liver fibrosis. Specifically,

lincRNA-ROR mediated the interaction between miR-145

and ZEB2, which is a transcription factor that

promotes HSC activation and fibrosis. By modulating

this pathway, lincRNA-ROR was able to regulate the

expression of HERC5, which is involved in the

modification of the p53 protein by interferon-stimulated genes (ISGs). This modification is

important for the activation of p53 and the induction

of apoptosis in activated HSCs, which can slow or

reverse the progression of liver fibrosis.

Our findings suggest that lincRNA-ROR may be a promising molecular target for the treatment of liver

fibrosis. By modulating its expression or activity, it

may be possible to slow or even reverse the

progression of this disease. Further studies are

needed to confirm these findings in human patients and

to develop effective therapeutic strategies

In addition to lincRNA-ROR, other potential molecular

targets have been identified for the treatment of

liver fibrosis. One such target is miR-29, which has

been shown to inhibit collagen synthesis and reduce

the severity of liver fibrosis in animal models.

Another target is galectin-3, a carbohydrate-binding

protein that plays a role in fibrosis by promoting the

activation of HSCs. Inhibition of galectin-3 has been

shown to reduce liver fibrosis in animal models.

In addition to targeting specific molecules, there are

also approaches that focus on modulating the immune

response to liver injury. For example, drugs that

inhibit TGF-β signaling have been shown to reduce

liver fibrosis by blocking the activation of HSCs and

promoting the activity of immune cells that help to

resolve fibrosis. Similarly, modulation of the gut

microbiome has been shown to have a potential

therapeutic effect on liver fibrosis, as the gut

microbiome has been shown to play a role in the development and progression of this disease.

While there are a number of potential molecular

targets and therapeutic strategies for the treatment

of liver fibrosis, there is still much to be learned

about this disease. Further studies are needed to

fully understand the molecular mechanisms that drive

liver fibrosis and to identify new therapeutic targets.

Additionally, clinical studies are needed to test the

safety and efficacy of novel therapies in human

patients. With continued research and development, it

is hoped that effective treatments for liver fibrosis

will become available to patients in the near future

Liver fibrosis is a major global health concern, with

millions of people affected worldwide. Despite

advances in medicine, there are currently no approved

treatments that can effectively cure liver fibrosis.

Therefore, there is a critical need for continued

research to advance our understanding of this disease

and develop new and effective therapeutic strategies.

One area of active research is the molecular

mechanisms that drive liver fibrosis. Researchers are

working to identify the key signaling pathways and

molecular targets that promote the deposition of

collagen and other extracellular matrix proteins in the liver, which are responsible for the scarring and

damage that occur in this disease. By understanding

the underlying mechanisms, it may be possible to

develop targeted therapies that can slow or even

reverse the progression of liver fibrosis.

Another area of focus is the identification of new

therapeutic targets for liver fibrosis. Researchers

are exploring a wide range of potential targets,

including growth factors, cytokines, and enzymes that

play a role in the disease process. Some promising

targets include signaling pathways involved in

fibrosis development, such as the TGF-β pathway, as

well as enzymes that break down the extracellular

matrix proteins responsible for scarring. By

identifying and targeting new pathways, it may be

possible to develop novel treatments that can halt or

even reverse the progression of liver fibrosis.

Clinical studies are also a critical component of

liver fibrosis research. While preclinical studies in

animal models are essential for understanding the

underlying mechanisms and identifying potential

therapeutic targets, it is important to test these

treatments in human patients to determine their safety

and efficacy. Several promising therapies are

currently being evaluated in clinical trials, including antifibrotic agents, immunomodulators, and

cell-based therapies. These studies will play an

important role in advancing our understanding of liver

fibrosis and in the development of effective

treatments for this debilitating disease.

In addition to developing new therapies, there is a

need for improved diagnostics and screening tools for

liver fibrosis. Current diagnostic methods, such as

liver biopsy, are invasive and may not be suitable for

all patients. There is a need for non-invasive methods

to accurately diagnose and monitor the progression of

liver fibrosis. Several non-invasive tests, such as

transient elastography and serum biomarker assays, are

currently in use or under development and may prove to

be valuable tools for screening and monitoring

patients with liver fibrosis.

In conclusion, liver fibrosis remains a significant

challenge for the medical community. The molecular

mechanisms that drive this disease are complex and not

fully understood, and there are currently no approved

treatments that can cure or halt its progression.

However, continued research and development of new

therapies, as well as improved diagnostic and

screening tools, hold promise for improving the lives

of patients with liver fibrosis in the future 总之，肝纤维化对医疗界仍然是一项重大挑战。驱动该疾病的分子机制非常复杂且尚未完全理解，目前还没有批准的治疗方案可以治愈或阻止其进展。然而，继续研究和开发新的治疗方法以及改进诊断和筛查工具，有望在将来改善肝纤维化患者的生活

本文标签： 纤维化治疗作用机制修饰