Department of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Head and Neck Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
J Immunol Res. 2022 May 28;2022:5819295. doi: 10.1155/2022/5819295. eCollection 2022.
MicroRNA-328-3p (miR-328-3p) plays a critical role in mediating the progression of multiple types of cancers. To date, no study has concentrated on the molecular mechanism of miR-328-3p in mediating stomach adenocarcinoma (STAD). In this study, it was found that miR-328-3p was downregulated in STAD, and inhibition of miR-328-3p significantly promoted the growth, migration, invasion, and stemness of STAD cells, while miR-328-3p overexpression exerted reverse effects. Through bioinformatics analysis, it was uncovered that a cluster of differentiation 44 (CD44) was upregulated in STAD and closely associated with the prognosis of STAD patients. Mechanistically, we identified CD44 as the target gene of miR-328-3p. Notably, knockdown of CD44 abolished the promoting function of miR-328-3p inhibitor in the development of STAD. Moreover, myeloid zinc finger protein 1 (MZF1) was confirmed as an upstream transcription factor for miR-328-3p, which is involved in enhancing miR-328-3p expression. In addition, the role of MZF1 downregulation in the malignant traits of STAD cells was blocked by miR-328-3p overexpression. More importantly, upregulation of miR-328-3p efficiently suppressed STAD tumor growth . Collectively, our findings illustrated that MZF1-mediated miR-328-3p acted as a cancer suppressor in STAD progression via regulation of CD44, which suggested the possibility of the MZF1/miR-328-3p/CD44 axis as a novel promising therapeutic candidate for STAD.
微小 RNA-328-3p（miR-328-3p）在介导多种类型癌症的进展中起着关键作用。迄今为止，尚无研究集中于 miR-328-3p 介导胃腺癌（STAD）的分子机制。在本研究中，发现 miR-328-3p 在 STAD 中下调，抑制 miR-328-3p 显著促进 STAD 细胞的生长、迁移、侵袭和干性，而 miR-328-3p 过表达则产生相反的效果。通过生物信息学分析，发现 CD44 在 STAD 中上调，并与 STAD 患者的预后密切相关。从机制上讲，我们确定 CD44 是 miR-328-3p 的靶基因。值得注意的是，敲低 CD44 消除了 miR-328-3p 抑制剂在 STAD 发展中的促进作用。此外，髓样锌指蛋白 1（MZF1）被确认为 miR-328-3p 的上游转录因子，参与增强 miR-328-3p 的表达。此外，miR-328-3p 过表达阻断了 MZF1 下调对 STAD 细胞恶性特征的作用。更重要的是，miR-328-3p 的上调有效地抑制了 STAD 肿瘤的生长。综上所述，我们的研究结果表明，MZF1 介导的 miR-328-3p 通过调节 CD44 在 STAD 进展中发挥抑癌作用，提示 MZF1/miR-328-3p/CD44 轴作为 STAD 新型有前途的治疗候选物的可能性。
