Abnormal Spindle-like Microcephaly-associated Protein Enhances Cell Invasion Through Wnt/β-catenin-dependent Regulation of Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer Cells

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2021 May 20

PMID 34012593

Citations 3

Authors

Chunwei Xia

Xiaofeng Xu

Yiyan Ding

Cunjun Yu

Jianbing Qiao

Ping Liu

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer is one of the most common cancer worldwide, invasion and metastasis are still the bottleneck in the clinical setting. More diagnostic markers and drug targets need to be clarified. Therefore, we screened abnormal spindle-like microcephaly-associated protein () as our candidate gene, which is associated with the poor prognosis. The aim of the present study was to understand the roles of in cell invasion in non-small cell lung cancer (NSCLC).

Methods: Gene Expression Omnibus (GEO) datamining was used to identify . Transwell invasion assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to discover the molecular functions of . Overexpression and small interfering mediated knockdown techniques have been used to study the cell invasion hallmarks of cancer.

Results: stood out among all the candidate genes from GEO datamining. in lung cancer tissues has been associated with poor overall survival rate. The protein levels of has been validated using lung cancer patients' tissues, which upregulation of expression has been found in lung cancer patients. Silencing of decreased the cell invasion reflected by epithelial-mesenchymal transition (EMT) biomarkers: downregulation of vimentin and upregulation of E-cadherin. Matrix metalloproteinase (MMP) 2/9 protein levels were also affected upon transient knockdown of . Furthermore, the suppression of markedly inhibited the Wnt/β-catenin signaling pathway . The ectopic expression of had the opposite effect. The inhibition of β-catenin in -overexpressing lung cancer cells reduced the expression of EMT markers. The inhibitory effects on the Wnt/β-catenin signaling pathway were attenuated in cancer cells when was silenced. These findings demonstrated that the silencing of strongly reduced cell invasion in lung cancer.

Conclusions: promoted NSCLC invasion through EMT and by affecting the MMP family of proteins. The Wnt/β-catenin signaling pathway played an indispensable role in the -mediated NSCLC EMT-invasion cascade.

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