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MIB2 通过调控细胞周期控制通路促进非小细胞肺癌的进展。

MIB2 promotes the progression of non-small cell lung cancer by regulating cell cycle control pathways.

机构信息

¹Department of Oncology, Huashan Hospital Fudan University, 12 Middle Urumqi Road, Shanghai, 200000, China.

Shanghai Medical College, Fudan University, Shanghai, 200032, China.

出版信息

Genes Genomics. 2023 Sep;45(9):1143-1152. doi: 10.1007/s13258-023-01423-4. Epub 2023 Jul 12.

Abstract

BACKGROUND

Although numerous measures have been used to improve the outcome of lung cancer patients, lung cancer, as the second most common diagnosed cancer, is still the main cause of cancer death. It becomes increasingly urgent for us to deeply deplore the molecular mechanism of lung cancer and to discover the potential therapeutic targets. In our study, we are dedicated to discovering the role of MIB2 in lung cancer development.

METHODS

The public databases were used to compare the expression level of MIB2 in cancer and non-cancer tissue. We analyzed the expression of MIB2 in lung cancer samples by performing Rt-PCR and western blot. We carried out CCK8 and clone assays to study the influence of MIB2 in lung cancer proliferation. The transwell assays and wound healing assays were implemented to study the function of MIB2 in metastasis and invasion. Proteins of cell cycle control pathways are detected to verify the potential mechanism of MIB2 in lung cancer progression.

RESULTS

MIB2 is up regulated in lung cancer tissue compared to adjacent normal lung tissue according to both public databases and our clinical lung cancer samples. Knockdown of MIB2 inhibits proliferation, metastasis, and invasion of lung cancer cell lines. Cyclins and cyclin dependent kinases (CDK) including CDK2, CDK4, and cyclinB1 were down regulated in MIB2 knockdown cells.

CONCLUSION

Our results prove that MIB2 acts as a driver in NSCLC tumorigenesis by regulating cell cycle control pathways.

摘要

背景

尽管已经采用了许多措施来改善肺癌患者的预后,但作为第二大常见诊断癌症的肺癌,仍然是癌症死亡的主要原因。我们迫切需要深入研究肺癌的分子机制,并发现潜在的治疗靶点。在我们的研究中,我们致力于发现 MIB2 在肺癌发展中的作用。

方法

使用公共数据库比较 MIB2 在癌症和非癌症组织中的表达水平。通过进行 Rt-PCR 和 Western blot 分析来研究 MIB2 在肺癌样本中的表达。通过 CCK8 和克隆实验来研究 MIB2 对肺癌增殖的影响。通过 Transwell 实验和划痕愈合实验来研究 MIB2 在转移和侵袭中的功能。检测细胞周期控制通路的蛋白以验证 MIB2 在肺癌进展中的潜在机制。

结果

根据公共数据库和我们的临床肺癌样本,MIB2 在肺癌组织中上调,与相邻的正常肺组织相比。MIB2 敲低抑制肺癌细胞系的增殖、转移和侵袭。MIB2 敲低细胞中细胞周期蛋白和细胞周期蛋白依赖性激酶(CDK),包括 CDK2、CDK4 和 cyclinB1,下调。

结论

我们的结果证明,MIB2 通过调节细胞周期控制通路在 NSCLC 肿瘤发生中起驱动作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68a5/10435422/8032870f51dc/13258_2023_1423_Fig1_HTML.jpg

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