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在食管鳞状细胞癌中,前蛋白转化酶枯草溶菌素9(PCSK9)通过促进趋化因子配体25(CCL25)的分泌来促进肿瘤细胞增殖和迁移。

PCSK9 promotes tumor cell proliferation and migration by facilitating CCL25 secretion in esophageal squamous cell carcinoma.

作者信息

Wang Haijun, Guo Qiang, Wang Mingbo, Liu Changjiang, Tian Ziqiang

机构信息

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050010, P.R. China.

Department of Thoracic Surgery, Xingtai People's Hospital, Xingtai, Hebei 054000, P.R. China.

出版信息

Oncol Lett. 2023 Oct 4;26(5):500. doi: 10.3892/ol.2023.14086. eCollection 2023 Nov.

DOI:10.3892/ol.2023.14086
PMID:37854863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10579978/
Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves an important role in maintaining plasma cholesterol levels, and fatty acid metabolism is involved in the progression of various types of cancer. In the present study, the role of PCSK9 in the development of esophageal squamous cell carcinoma (ESCC) was investigated. PCSK9 expression was compared between ESCC and normal esophageal epithelial tissues using reverse transcription-quantitative PCR. In addition, the association between PCSK9 expression and clinical staging and prognosis was assessed by immunohistochemistry. The effects of PCSK9 overexpression or knockdown on cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. The invasion and migration of cancer cells was assessed using wound healing and Transwell assays. Western blotting was performed to evaluate changes in the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. ELISA was performed to detect the effects of PCSK9 on chemokine (C-C motif) ligand 25 (CCL25) secretion. The results revealed that PCSK9 was highly expressed in ESCC tissues compared with that in normal esophageal tissues, and the high expression of PCSK9 was associated with a poor prognosis. Furthermore, PCSK9 could promote the proliferation, migration and invasion of ESCC cells . Mechanistically, PCSK9 could promote EMT by secreting CCL25. In conclusion, patients with ESCC may benefit from a novel therapeutic strategy based on these findings.

摘要

前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)在维持血浆胆固醇水平中起重要作用,并且脂肪酸代谢参与各种类型癌症的进展。在本研究中,研究了PCSK9在食管鳞状细胞癌(ESCC)发生发展中的作用。使用逆转录定量PCR比较了ESCC组织和正常食管上皮组织中PCSK9的表达。此外,通过免疫组织化学评估PCSK9表达与临床分期和预后之间的关联。使用细胞计数试剂盒-8和集落形成试验评估PCSK9过表达或敲低对细胞增殖的影响。使用伤口愈合试验和Transwell试验评估癌细胞的侵袭和迁移。进行蛋白质印迹以评估上皮-间质转化(EMT)相关蛋白表达水平的变化。进行酶联免疫吸附测定(ELISA)以检测PCSK9对趋化因子(C-C基序)配体25(CCL25)分泌的影响。结果显示,与正常食管组织相比,PCSK9在ESCC组织中高表达,并且PCSK9的高表达与不良预后相关。此外,PCSK9可促进ESCC细胞的增殖、迁移和侵袭。机制上,PCSK9可通过分泌CCL25促进EMT。总之,基于这些发现,ESCC患者可能从新的治疗策略中获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/7f4f943dd908/ol-26-05-14086-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/7ef42803b439/ol-26-05-14086-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/1078272e7e07/ol-26-05-14086-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/a965b119fbbc/ol-26-05-14086-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/0f6f87cf710b/ol-26-05-14086-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/7f4f943dd908/ol-26-05-14086-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/7ef42803b439/ol-26-05-14086-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/1078272e7e07/ol-26-05-14086-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/a965b119fbbc/ol-26-05-14086-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/0f6f87cf710b/ol-26-05-14086-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa3d/10579978/7f4f943dd908/ol-26-05-14086-g04.jpg

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