Division of Gastroenterology, Department of Internal Medicine, Kangnam Sacred-Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul Korea.
Yonsei University College of Medicine, 50-Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.
Int J Med Sci. 2020 Feb 24;17(6):693-701. doi: 10.7150/ijms.42654. eCollection 2020.
In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.
在我们之前的研究中，我们发现了三个 miRNA（hsa-miR-421、hsa-miR-29b-1-5p 和 hsa-miR-27b-5p）和两个 mRNA（FBXO11 和 CREBZF），它们可能在胃腺癌（GAC）从癌前腺瘤发展中发挥重要作用。然而，这些 miRNA 的表达和功能尚未得到很好的描述。我们使用免疫组织化学染色和 miRNA 杂交技术，研究了 CREBZF 和 miRNA 作为低/高级别发育不良和早期胃癌患者胃癌进展的潜在生物标志物的作用。考虑到靶标可能在 GC 中发生调节，我们通过 RT-PCR 和 Western blot 分析分析了胃癌细胞系中的 CREBZF 表达。与 SNU-NCC-19 相比，在 MKN-74 胃癌细胞中观察到随着 miRNA 表达的增加，CREBZF 的表达降低。接下来，通过 miRNA/anti-miRNA 调节研究了 CREBZF 在 MKN-74 胃癌细胞中的作用对细胞活力和迁移的影响。此外，我们发现 hsa-miR-421/hsa-miR-29b-1-5p 靶向 CREBZF，并可能在 MKN-74 细胞的迁移中发挥重要作用。这项研究表明，hsa-miR-421/hsa-miR-29b-1-5p 抑制 CREBZF 的增加可能对预防胃癌早期进展很重要。
