Wu Dong-Mei, Wen Xin, Han Xin-Rui, Wang Shan, Wang Yong-Jian, Shen Min, Fan Shao-Hua, Zhang Zi-Feng, Shan Qun, Li Meng-Qiu, Hu Bin, Lu Jun, Chen Gui-Quan, Zheng Yuan-Lin
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China; College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China; College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
Mol Ther Nucleic Acids. 2019 Jun 7;16:229-245. doi: 10.1016/j.omtn.2019.02.022. Epub 2019 Mar 1.
Pancreatic cancer is a lethal malignancy with relatively few effective therapies. Recent investigations have highlighted the role of microRNAs (miRNAs) as crucial regulators in various tumor processes including tumor progression. Hence the current study aimed to investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-126-3p (miR-126-3p) in pancreatic cancer. Initially, miRNA candidates and related genes associated with pancreatic cancer were screened. PANC-1 cells were transfected with miR-126-3p or silenced a disintegrin and a metalloproteinase-9 (ADAM9) to examine their regulatory roles in pancreatic cancer cells. Additionally, exosomes derived from BMSCs were isolated and co-cultured with pancreatic cancer cells to elucidate the effects of exosomes in pancreatic cancer. Furthermore, the effects of overexpressed miR-126-3p derived from BMSCs exosomes on proliferation, migration, invasion, apoptosis, tumor growth, and metastasis of pancreatic cancer cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo. Restored miR-126-3p was observed to suppress pancreatic cancer through downregulating ADAM9. Notably, overexpressed miR-126-3p derived from BMSCs exosomes inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells, and promoted their apoptosis both in vitro and in vivo. Taken together, the key findings of the study indicated that overexpressed miR-126-3p derived from BMSCs exosomes inhibited the development of pancreatic cancer through the downregulation of ADAM9, highlighting the potential of miR-126-3p as a novel biomarker for pancreatic cancer treatment.
胰腺癌是一种致命的恶性肿瘤，有效的治疗方法相对较少。最近的研究强调了微小RNA（miRNA）在包括肿瘤进展在内的各种肿瘤过程中作为关键调节因子的作用。因此，本研究旨在探讨骨髓间充质干细胞（BMSC）衍生的外泌体微小RNA-126-3p（miR-126-3p）在胰腺癌中的作用。首先，筛选与胰腺癌相关的miRNA候选物和相关基因。用miR-126-3p转染PANC-1细胞或沉默解整合素和金属蛋白酶-9（ADAM9），以研究它们在胰腺癌细胞中的调节作用。此外，分离出BMSC衍生的外泌体并与胰腺癌细胞共培养，以阐明外泌体在胰腺癌中的作用。此外，结合体内慢病毒包装的miR-126-3p，分析BMSC外泌体来源的过表达miR-126-3p对胰腺癌细胞增殖、迁移、侵袭、凋亡、肿瘤生长和转移的影响。观察到恢复的miR-126-3p通过下调ADAM9来抑制胰腺癌。值得注意的是，BMSC外泌体来源的过表达miR-126-3p在体外和体内均抑制胰腺癌细胞的增殖、侵袭和转移，并促进其凋亡。综上所述，该研究的主要发现表明，BMSC外泌体来源的过表达miR-126-3p通过下调ADAM9抑制胰腺癌的发展，突出了miR-126-3p作为胰腺癌治疗新生物标志物的潜力。
