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KIF18B 的上调通过激活 CDCA8/mTORC1 通路促进食管鳞癌细胞的恶性表型。

Upregulation of KIF18B facilitates malignant phenotype of esophageal squamous cell carcinoma by activating CDCA8/mTORC1 pathway.

机构信息

Gastroenterology Department, Yaan People's Hospital, Ya'an, China.

Cardiology Department, Yaan People's Hospital, Ya'an, China.

出版信息

J Clin Lab Anal. 2022 Oct;36(10):e24633. doi: 10.1002/jcla.24633. Epub 2022 Sep 9.

DOI:10.1002/jcla.24633
PMID:36085568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9550975/
Abstract

BACKGROUND

Kinesin family member 18B (KIF18B) has been regarded as an oncogene that is abnormally overexpressed in some cancers, but its mechanism in esophageal squamous cell carcinoma (ESCC) remains unclear, which is thereby investigated in this study.

METHODS

Bioinformatics analysis was performed to analyze the expression of KIF18B in esophageal carcinoma (ESCA). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect KIF18B expression in ESCC cells. After KIF18B overexpression or cell division cycle associated 8 (CDCA8) deficiency, ESCC cells were subjected to determination of qRT-PCR, Western blot, cell counting kit-8 assay, flow cytometry, wound healing, and Transwell assay. The mechanism of KIF18B in the mechanistic target of rapamycin complex 1 (mTORC1) pathway was detected by Western blot.

RESULTS

KIF18B was overexpressed in ESCA samples and ESCC cells. Upregulation of KIF18B enhanced the viability, accelerated cell cycle by elevating CDK4 and Cyclin D3 levels as well as promoted the migration and invasion by decreasing E-cadherin level and increasing Vimentin and N-cadherin levels in ESCC cells, which was counteracted by CDCA8 silencing. The expression of CDCA8 in ESCC cells was upregulated by KIF18B overexpression. KIF18B overexpression activated the mTORC1 pathway by upregulating phosphorylated (p)-/p70S6K and p-/mTOR levels in the ESCC cells, which was reversed by CDCA8 silencing.

CONCLUSION

KIF18B overexpression promotes the proliferation, migration, and invasion of ESCC cells via CDCA8-mediated mTORC1 signaling pathway in vitro.

摘要

背景

驱动蛋白家族成员 18B(KIF18B)已被视为一种在某些癌症中异常过表达的癌基因,但在食管鳞状细胞癌(ESCC)中的机制尚不清楚,因此本研究对此进行了探讨。

方法

通过生物信息学分析,分析 KIF18B 在食管癌(ESCA)中的表达。采用实时定量聚合酶链反应(qRT-PCR)检测 ESCC 细胞中 KIF18B 的表达。过表达 KIF18B 或敲低细胞分裂周期相关蛋白 8(CDCA8)后,通过 qRT-PCR、Western blot、细胞计数试剂盒-8 检测、流式细胞术、划痕愈合和 Transwell 实验检测 ESCC 细胞的活力、细胞周期、迁移和侵袭能力。通过 Western blot 检测 KIF18B 在雷帕霉素靶蛋白复合物 1(mTORC1)通路中的作用机制。

结果

KIF18B 在 ESCA 样本和 ESCC 细胞中高表达。上调 KIF18B 可增强 ESCC 细胞的活力,通过提高 CDK4 和 Cyclin D3 水平加速细胞周期,通过降低 E-cadherin 水平和增加 Vimentin 和 N-cadherin 水平促进迁移和侵袭,CDCA8 沉默可逆转上述作用。KIF18B 过表达可上调 ESCC 细胞中 CDCA8 的表达。KIF18B 过表达通过上调 ESCC 细胞中磷酸化(p)-/p70S6K 和 p-/mTOR 水平激活 mTORC1 通路,CDCA8 沉默可逆转这一作用。

结论

KIF18B 过表达通过 CDCA8 介导的 mTORC1 信号通路促进 ESCC 细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/ba740fb35226/JCLA-36-e24633-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/003f8d825abf/JCLA-36-e24633-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/fae65374f4f1/JCLA-36-e24633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/dfac45e378cb/JCLA-36-e24633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/7b46ad0d2900/JCLA-36-e24633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/85ed6c3886d1/JCLA-36-e24633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/ee2e20ccced1/JCLA-36-e24633-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/ba740fb35226/JCLA-36-e24633-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/003f8d825abf/JCLA-36-e24633-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/fae65374f4f1/JCLA-36-e24633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/dfac45e378cb/JCLA-36-e24633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/7b46ad0d2900/JCLA-36-e24633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/85ed6c3886d1/JCLA-36-e24633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/ee2e20ccced1/JCLA-36-e24633-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/9550975/ba740fb35226/JCLA-36-e24633-g006.jpg

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