靶向 AGTPBP1 可通过调节微管和 ERK 信号通路抑制胰腺癌的进展。

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Medicine Pub Date : 2024-08-11 DOI:10.1186/s10020-024-00892-x

Ding-Zhong Li, Zhe-Yu Yang, Asi Leng, Qian Zhang, Xiao-Dong Zhang, Yan-Chao Bian, Rui Xiao, Jian-Jun Ren

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引用次数: 0

摘要

背景AGTPBP1 是一种细胞膜羧肽酶，可从 α/β 管蛋白的 C 末端或侧链中裂解聚谷氨酸。虽然 AGTPBP1 的表达失调与非小细胞肺癌的发展有关，但其在胰腺癌（PC）中的具体作用和机制尚未完全明了。本研究探讨了 AGTPBP1 在体外和体内对胰腺癌的作用：方法：采用免疫组化方法检测 AGTPBP1 在 PC 和非癌组织中的表达。此外，我们还评估了 siRNA 介导的 AGTPBP1 体外和体内敲除后 PC 细胞的恶性行为。我们进行了 RNA 测序和生物信息学分析，以确定受 AGTPBP1 调控的差异表达基因：结果：我们发现 AGTPBP1 在 PC 组织中过表达，且 AGTPBP1 的高表达与肿瘤的位置密切相关。抑制 AGTPBP1 可显著降低体内和体外的细胞进展。此外，敲除AGTPBP1可通过ERK信号通路抑制ERK1/2、P-ERK1/2、MYLK和TUBB4B蛋白的表达：我们的研究表明，AGTPBP1可能是治疗PC的一个潜在靶点。

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Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.

Background: AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/β tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo.

Methods: Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1.

Results: We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway.

Conclusion: Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.