关键词: Hippo signaling pathway Lung Cancer MiR-762 SMAD3 TWIST1

Mesh : Humans Hippo Signaling Pathway Signal Transduction Lung Neoplasms / genetics Cell Line, Tumor MicroRNAs / genetics metabolism Chronic Disease Cell Proliferation / genetics Smad3 Protein / genetics metabolism Nuclear Proteins / genetics metabolism Twist-Related Protein 1 / genetics metabolism Protein Serine-Threonine Kinases / genetics metabolism Tumor Suppressor Proteins / genetics metabolism

来  源:   DOI:10.1038/s41598-024-58704-5   PDF(Pubmed)

Abstract:
MicroRNAs are small RNA molecules that have a significant role in translational repression and gene silencing through binding to downstream target mRNAs. MiR-762 can stimulate the proliferation and metastasis of various types of cancer. Hippo pathway is one of the pathways that regulate tissue development and carcinogenesis. Dysregulation of this pathway plays a vital role in the progression of cancer. This study aimed to evaluate the possible correlation between miR-762, the Hippo signaling pathway, TWIST1, and SMAD3 in patients with lung cancer, as well as patients with chronic inflammatory diseases. The relative expression of miR-762, MST1, LATS2, YAP, TWIST1, and SMAD3 was determined in 50 lung cancer patients, 30 patients with chronic inflammatory diseases, and 20 healthy volunteers by real-time PCR. The levels of YAP protein and neuron-specific enolase were estimated by ELISA and electrochemiluminescence immunoassay, respectively. Compared to the control group, miR-762, YAP, TWIST1, and SMAD3 expression were significantly upregulated in lung cancer patients and chronic inflammatory patients, except SMAD3 was significantly downregulated in chronic inflammatory patients. MST1, LATS2, and YAP protein were significantly downregulated in all patients. MiR-762 has a significant negative correlation with MST1, LATS2, and YAP protein in lung cancer patients and with MST1 and LATS2 in chronic inflammatory patients. MiR-762 may be involved in the induction of malignant behaviors in lung cancer through suppression of the Hippo pathway. MiR-762, MST1, LATS2, YAP mRNA and protein, TWIST1, and SMAD3 may be effective diagnostic biomarkers in both lung cancer patients and chronic inflammatory patients. High YAP, TWIST1, SMA3 expression, and NSE level are associated with a favorable prognosis for lung cancer.
摘要:
MicroRNA是通过与下游靶mRNA结合而在翻译抑制和基因沉默中具有重要作用的小RNA分子。MiR-762可以刺激各种类型癌症的增殖和转移。Hippo通路是调控组织发育和癌变的通路之一。该通路的失调在癌症的进展中起着至关重要的作用。本研究旨在评估miR-762与Hippo信号通路,肺癌患者的TWIST1和SMAD3,以及慢性炎症性疾病患者。miR-762、MST1、LATS2、YAP、在50例肺癌患者中测定了TWIST1和SMAD3,30例慢性炎症性疾病患者,和20名健康志愿者通过实时PCR。采用酶联免疫吸附试验和电化学发光法检测YAP蛋白和神经元特异性烯醇化酶的水平,分别。与对照组相比,miR-762,YAP,TWIST1和SMAD3表达在肺癌患者和慢性炎症患者中显著上调,除了SMAD3在慢性炎症患者中显著下调。所有患者的MST1、LATS2和YAP蛋白均显著下调。MiR-762与肺癌患者的MST1、LATS2和YAP蛋白呈显著负相关,与慢性炎症患者的MST1和LATS2呈显著负相关。MiR-762可能通过抑制Hippo途径参与诱导肺癌恶性行为。MiR-762,MST1,LATS2,YAPmRNA和蛋白,TWIST1和SMAD3可能是肺癌患者和慢性炎症患者的有效诊断生物标志物。HighYAP,TWIST1,SMA3表达,和NSE水平与肺癌的良好预后相关。
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