Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2127-2134. doi: 10.3892/mmr.2019.10451. Epub 2019 Jul 1.
T‑cell lymphoblastic lymphoma (T‑LBL) is an aggressive malignancy with poor prognosis due to frequent relapses. Previous studies have reported an association of the disease with abnormal chromosomal rearrangements, DNA copy number alterations and mutations in critical signaling factors, such as those in the Notch1 pathway; however, the molecular mechanisms underlying the development of the disease remain unclear, limiting the development of novel therapies. In the present study, gene expression was detected by qPCR and western blot analysis. Diagnostic analysis was performed by ROC curve. Cell proliferation, invasion and migration were analyzed by cell proliferation and Transwell assays. Gene interactions were analyzed using luciferase reporter assay. In the present study, it was observed that the expression levels of microRNA‑338‑3p (miR‑338‑3p) were reduced in patient lymphoma tissues and a T‑LBL cell line. Upregulation of its expression inhibited the migration and proliferation of cultured T‑LBL cells. Bioinformatics analysis of putative target mRNAs of miR‑338‑3p identified a direct binding site in the 3'‑untranslated of homeobox A3 (HOXA3). The levels of HOXA3 mRNA and protein were associated with those of miR‑338‑3p, and overexpression of HOXA3 promoted the malignant phenotype of T‑LBL cells. The results suggested that miR‑338‑3p may suppress the development of T‑LBL via the downregulation of oncogenic factors, such as HOXA3. The findings indicated that further investigation into miR‑338‑3p and the HOXA3 regulatory network may aid the development of novel therapeutic tools.
T 细胞淋巴母细胞淋巴瘤(T-LBL)是一种侵袭性恶性肿瘤,由于频繁复发,预后不良。先前的研究报道,该疾病与异常染色体重排、DNA 拷贝数改变以及关键信号因子(如 Notch1 通路)的突变有关;然而,疾病发展的分子机制尚不清楚,限制了新疗法的开发。在本研究中,通过 qPCR 和 Western blot 分析检测基因表达。通过 ROC 曲线进行诊断分析。通过细胞增殖和 Transwell 测定分析细胞增殖、侵袭和迁移。通过荧光素酶报告基因测定分析基因相互作用。在本研究中,观察到微 RNA-338-3p(miR-338-3p)在患者淋巴瘤组织和 T-LBL 细胞系中的表达水平降低。上调其表达抑制培养的 T-LBL 细胞的迁移和增殖。miR-338-3p 的假定靶 mRNA 的生物信息学分析鉴定了同源盒 A3(HOXA3)3'非翻译区的直接结合位点。HOXA3 mRNA 和蛋白的水平与 miR-338-3p 的水平相关,HOXA3 的过表达促进了 T-LBL 细胞的恶性表型。结果表明,miR-338-3p 可能通过下调致癌因子(如 HOXA3)抑制 T-LBL 的发展。研究结果表明,进一步研究 miR-338-3p 和 HOXA3 调控网络可能有助于开发新的治疗工具。