Li Yating, Wang Xing, Liu Xiaolong, Li Xiangjie, Zhang Jianling, Li Yulan
The First School of Clinical Medical, Lanzhou University, Lanzhou, Gansu, P.R. China.
The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, P.R. China.
PLoS One. 2024 Dec 31;19(12):e0316476. doi: 10.1371/journal.pone.0316476. eCollection 2024.
Gastric cancer (GC) is a highly malignant gastrointestinal tumor characterized by difficult early diagnosis and poor prognosis. Therefore, it is imperative to explore potential therapeutic targets for gastric cancer. PARP9 is abnormally expressed in a variety of tumors and is associated with tumor cell apoptosis and DNA damage. However, its relationship with GC has not been fully studied.
The expression and prognostic significance of PARP9 in gastric cancer (GC) were examined using bioinformatics approaches. Cell lines with either knockdown or overexpression of PARP9 were established through lentiviral transduction, and the role of PARP9 in the malignant phenotypes of GC cells was validated via CCK8 assays, wound healing assays, clonogenic assays, and Transwell migration experiments. Finally, alterations in downstream targets and signaling pathways following changes in PARP9 expression were analyzed through RNA sequencing.
PARP9 is highly expressed in GC tissues and is associated with poor prognosis. PARP9 knockdown can significantly inhibit the proliferation, invasion and migration of GC cells, and increase the apoptosis and DNA damage of GC cells. The therapeutic process of PARP9 in GC may be realized by synergistic interaction with SOX6 through MAPK signaling pathway.
Our study reveals a potential link between PARP9 and GC, providing a new target for the treatment of GC.
胃癌（GC）是一种高度恶性的胃肠道肿瘤，其特征为早期诊断困难且预后不良。因此，探索胃癌的潜在治疗靶点势在必行。聚（ADP-核糖）聚合酶9（PARP9）在多种肿瘤中异常表达，且与肿瘤细胞凋亡和DNA损伤相关。然而，其与胃癌的关系尚未得到充分研究。
采用生物信息学方法检测PARP9在胃癌（GC）中的表达及预后意义。通过慢病毒转导建立PARP9敲低或过表达的细胞系，并通过CCK8检测、伤口愈合检测、克隆形成检测和Transwell迁移实验验证PARP9在GC细胞恶性表型中的作用。最后，通过RNA测序分析PARP9表达变化后下游靶点和信号通路的改变。
PARP9在GC组织中高表达，且与预后不良相关。PARP9敲低可显著抑制GC细胞的增殖、侵袭和迁移，并增加GC细胞的凋亡和DNA损伤。PARP9在GC中的治疗过程可能通过与SOX6通过丝裂原活化蛋白激酶（MAPK）信号通路协同相互作用来实现。
我们的研究揭示了PARP9与GC之间的潜在联系，为GC的治疗提供了新的靶点。
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