Lentivirus-mediated inhibition of USP39 suppresses the growth of gastric cancer cells via PARP activation
Lentivirus-mediated inhibition of USP39 suppresses the growth of gastric cancer cells via PARP activation
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DOI：
10.3892/mmr.2016.5252
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Yu, Pengfei
中科院分区：
文献类型：
--
作者：
Wang, Xinbao;Yu, Qiming;Yu, Pengfei
胃癌（GC）是全球癌症相关死亡的第二大常见原因。泛素特异性肽酶39 （USP39）在mRNA加工中起重要作用，并参与乳腺癌细胞的生长。然而，USP39在GC中的作用仍有待研究，这是本研究的目的。构建了以USP39为靶点的短发夹RNA慢病毒，并将其转染到MGC80-3细胞中。MTT和克隆生成实验表明，抑制USP39的表达可显著降低MGC80-3细胞的增殖和集落形成能力。此外，流式细胞术细胞周期分析显示，USP39的抑制诱导G2/ m期阻滞，而细胞内信号阵列显示，USP39敲除后，Asp214处PARP的切割增加。这些结果表明USP39参与了胃癌的增殖，可能作为胃癌治疗的分子靶点。
Gastric cancer (GC) is the second most common cause of cancer-associated mortality worldwide. Ubiquitin-specific peptidase 39 (USP39) has important roles in mRNA processing and has been reported to be involved in the growth of breast cancer cells. However, the roles of USP39 in GC have remained to be investigated, which was the aim of the present study. A lentivirus expressing short hairpin RNA targeting USP39 was constructed and transfected into MGC80-3 cells. Suppression of USP39 expression significantly decreased the proliferation and colony forming ability of MGC80-3 cells as indicated by an MTT and a clonogenic assay, respectively. In addition, flow cytometric cell cycle analysis revealed that depression of USP39 induced G2/M-phase arrest, while an intracellular signaling array showed that the cleavage of PARP at Asp214 was increased following USP39 knockdown. These results suggested that USP39 is involved in the proliferation of GCs and may be utilized as a molecular target for GC therapy.