Department of Gastroenterology, Xinxiang Central Hospital, Xinxiang, Henan, China.
Department of Endocrinology, Xinxiang Central Hospital, Xinxiang, Henan, China.
J Biochem Mol Toxicol. 2021 Jul;35(7):e22782. doi: 10.1002/jbt.22782. Epub 2021 Apr 25.
MicroRNAs (miRs) are vital in the development of pancreatic cancer (PC) targeting several cellular processes. This study was aimed at evaluating the function of miR-125b and the mechanism involved in PC. Cell migration, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and Bromodeoxyuridine/5-bromo-2'-deoxyuridine (BrdU) study was done to establish the migration capability, cell viability, and cell proliferation, respectively. Binding sites for miR-125b were recognized by luciferase assay, and the expression of protein by Western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. The study showed that expression of miR-125b was elevated in PC cells and tissues and was correlated to proliferation and migration of cells. Also, overexpression of miR-125b encouraged migration, metastasis, and proliferation of BxPC-3 cells, and suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the three prime untranslated region (3'-UTR) activating hypoxia-inducible factor 1α (HIF1α). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. The miR-125b-TXNIP-HIF1α pathway may serve as a useful strategy for diagnosing and treating PC.
微小 RNA(miRs)在胰腺癌(PC)的发展中起着至关重要的作用,靶向多个细胞过程。本研究旨在评估 miR-125b 的功能及其在 PC 中涉及的机制。细胞迁移、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)和溴脱氧尿苷/5-溴-2'-脱氧尿苷(BrdU)研究分别用于建立迁移能力、细胞活力和细胞增殖。通过荧光素酶测定法识别 miR-125b 的结合位点,通过 Western blot 和免疫荧光测定法检测蛋白的表达。通过 BALB/c 裸鼠异种移植小鼠进行体内研究,以评估 miR-125b 的功能。研究表明,miR-125b 在 PC 细胞和组织中的表达上调,与细胞的增殖和迁移相关。此外,miR-125b 的过表达促进了 BxPC-3 细胞的迁移、转移和增殖,而抑制则逆转了这一过程。我们还注意到,硫氧还蛋白相互作用蛋白(TXNIP)是 miR-125b 的潜在靶标。研究结果还表明,miR-125b 通过直接结合到三磷酸未翻译区(3'-UTR)来负调控 TXNIP 的表达,从而激活缺氧诱导因子 1α(HIF1α)。在研究 HIF1α 和 TXNIP 之间的关系时,我们发现 TXNIP 通过与 HIF1α 形成复合物导致 HIF1α 的降解和输出。miR-125b-TXNIP-HIF1α 通路可能成为诊断和治疗 PC 的一种有用策略。