Department of Gastroenterology, The Chinese People's Liberation Army Navy 971 Hospital, Qingdao, China.
J Clin Lab Anal. 2020 Jun;34(6):e23215. doi: 10.1002/jcla.23215. Epub 2020 Feb 5.
CircMAN2B2 is a newly discovered circRNA that has been found to be an oncogene in lung cancer and glioma. The present study was designed to reveal the role of circMAN2B2 in gastric carcinoma (GC).
qRT-PCR method was utilized to examine circMAN2B2 expression in GC tissues and paracancerous tissues. Next, circMAN2B2 expression in SNU-16 and AGS cells was silenced by transfection. CCK-8 assay, colony formation assay, flow cytometer, Transwell assay, and Western blot were conducted for testing cell phenotype changes. Further, the downstream genes and signaling were uncovered by qRT-PCR and Western blot.
As relative to paracancerous tissues, circMAN2B2 was high-expressed in GC tissues. Silence of circMAN2B2 clearly declined SNU-16 and AGS cells viability, survival, migration but enhanced apoptosis. Meanwhile, silence of circMAN2B2 induced the cleavage of caspases (-3 and -9), down-regulation of MMPs (-2 and -9), and up-regulation of miR-145. The impacts of circMAN2B2 silence toward SNU-16 and AGS cells were attenuated by miR-145 silence. Moreover, circMAN2B2 silence deactivated PI3K, AKT while activated JNK through regulating miR-145.
This work presented the oncogenic function of circMAN2B2 in GC cells growth and migration. CircMAN2B2 exerted its function possibly through regulating miR-145 as well as PI3K/AKT and JNK pathways.
CircMAN2B2 是一种新发现的 circRNA,已被发现是肺癌和神经胶质瘤中的致癌基因。本研究旨在揭示 circMAN2B2 在胃癌(GC)中的作用。
利用 qRT-PCR 方法检测 GC 组织和癌旁组织中 circMAN2B2 的表达。接下来,通过转染沉默 SNU-16 和 AGS 细胞中的 circMAN2B2 表达。通过 CCK-8 测定、集落形成测定、流式细胞术、Transwell 测定和 Western blot 进行细胞表型变化测试。进一步通过 qRT-PCR 和 Western blot 揭示下游基因和信号通路。
与癌旁组织相比,circMAN2B2 在 GC 组织中高表达。沉默 circMAN2B2 明显降低了 SNU-16 和 AGS 细胞的活力、存活、迁移能力,但增强了细胞凋亡。同时,沉默 circMAN2B2 诱导了 caspase(-3 和 -9)的切割、MMPs(-2 和 -9)的下调以及 miR-145 的上调。miR-145 沉默减弱了 circMAN2B2 沉默对 SNU-16 和 AGS 细胞的影响。此外,circMAN2B2 沉默通过调节 miR-145 来激活 JNK,同时抑制 PI3K/AKT。
本研究揭示了 circMAN2B2 在 GC 细胞生长和迁移中的致癌作用。circMAN2B2 可能通过调节 miR-145 以及 PI3K/AKT 和 JNK 通路发挥其功能。