Silencing of LAMC2 Reverses Epithelial Mesenchymal Transition and Inhibits Progression in Pancreatic Ductal Adenocarcinoma via Inactivation of the NF-κB Signaling Pathway.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Lijuan Huang, Yan Han, Qingmin Zhou, Zhihao Sun, Jianhui Yan
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引用次数: 0

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult to treat of all malignancies. Multimodality regimens provide only short-term symptomatic improvement with minor impact on survival, underscoring the urgent need for novel therapeutics and treatment strategies for PDAC. We screened out the highly expressed gene LAMC2 in PDAC tissues through the GEO online database, and further demonstrated that it is related to the poor prognosis of PDAC patients. Next, we investigated the effect of LAMC2 in the development and metastasis of PDAC by silencing LAMC2 expression in PDAC cells. The results showed that silencing of LAMC2 inhibited the proliferation, invasion and metastasis, and promoted apoptosis of PDAC cells, silencing of LAMC2 also reversed the epithelial mesenchymal transition (EMT) and suppressed the activation of NF-κB signaling pathway. Our results identify LAMC2 as a pivotal regulator of PDAC malignant progression, and its overexpression is sufficient to confer the characteristically aggressive clinical features of this disease.

沉默 LAMC2 可通过抑制 NF-κB 信号通路逆转上皮间充质转化并抑制胰腺导管腺癌的进展
胰腺导管腺癌(PDAC)仍然是最难治疗的恶性肿瘤之一。多模式疗法只能在短期内改善症状,对存活率的影响微乎其微,这凸显了对 PDAC 新型疗法和治疗策略的迫切需求。我们通过 GEO 在线数据库筛选出了 PDAC 组织中的高表达基因 LAMC2,并进一步证明它与 PDAC 患者的不良预后有关。接下来,我们通过沉默PDAC细胞中LAMC2的表达,研究了LAMC2在PDAC发病和转移中的作用。结果显示,沉默LAMC2可抑制PDAC细胞的增殖、侵袭和转移,并促进其凋亡;沉默LAMC2还可逆转上皮间质转化(EMT),抑制NF-κB信号通路的激活。我们的研究结果表明,LAMC2是PDAC恶性进展的关键调控因子,它的过表达足以使这种疾病具有典型的侵袭性临床特征。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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