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抑制 SMAD4 表达水平,从而抑制结肠癌的生长和转移。

inhibits growth and metastasis in colon cancer by down-regulating SMAD4.

机构信息

Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.

School of Public Health, Jilin University, Changchun, Jilin, P.R. China.

出版信息

Biosci Rep. 2019 Mar 1;39(3). doi: 10.1042/BSR20181895. Print 2019 Mar 29.

Abstract

MicroRNAs (MiRs) are thought to display regulator action in tumor suppression and oncogenesis. plays an important role in the development of various cancers, such as colorectal cancer, breast cancer, and lung cancer, by targetting different molecules potentially involved in many signaling pathways. SMAD4 is a common signaling during tumor progression, and it can inhibit cell proliferation and promote cell motility in most epithelial cells. The present study focused on the effect of and SMAD4 on colon cancer in order to find the novel gene therapy target for the treatment of colon cancer. Quantitative real-time polymerase chain reaction was used to assess the expression level of in colon cancer tissues and SW620 cells. MTT assay, scratch test, and transwell assay were used to evaluate cell proliferation, migration, and invasion, respectively. Moreover, luciferase assays were utilized to identify the predictive effect of on SMAD4. Western blotting was performed to determine the relative expression of protein related to SMAD4. We found level was significantly lower in colon cancer tissues and SW620 cells. Moreover, SMAD4 level, both in mRNA and protein, was obviously elevated in colon cancer tissues. Further, mimics treatment inhibited cells proliferation, invasion, and migration. Fluorescence intensity of mimics group in wild type cells was decreased. mimics repressed the SMAD4 expression both in mRNA and protein. These findings about /SMAD4 pair provide a novel therapeutic method for colon cancer patients.

摘要

微小 RNA(miRs)被认为在肿瘤抑制和致癌作用中发挥调节作用。 在靶向参与许多信号通路的不同分子方面,通过靶向不同的分子,在各种癌症的发展中,如结直肠癌、乳腺癌和肺癌中发挥重要作用。SMAD4 是肿瘤进展过程中的常见信号转导因子,它可以抑制大多数上皮细胞中的细胞增殖并促进细胞迁移。本研究旨在研究 miR-494 和 SMAD4 对结肠癌的影响,以期为结肠癌的治疗找到新的基因治疗靶点。实时定量聚合酶链反应用于评估结肠癌组织和 SW620 细胞中 miR-494 的表达水平。MTT 测定、划痕试验和 Transwell 测定分别用于评估细胞增殖、迁移和侵袭。此外,还利用荧光素酶测定来鉴定 miR-494 对 SMAD4 的预测作用。Western blot 用于确定与 SMAD4 相关的蛋白的相对表达。我们发现 miR-494 在结肠癌组织和 SW620 细胞中的水平明显降低。此外,结肠癌组织中 SMAD4 的水平,无论是在 mRNA 还是蛋白水平,都明显升高。进一步的,miR-494 模拟物处理抑制细胞增殖、侵袭和迁移。野生型细胞中 miR-494 模拟物组的荧光强度降低。miR-494 模拟物抑制 SMAD4 的表达,无论是在 mRNA 还是蛋白水平。miR-494/SMAD4 对的这些发现为结肠癌患者提供了一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa8e/6395301/fb7e49ac33b1/bsr-39-bsr20181895-g1.jpg

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