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HHIP overexpression inhibits the proliferation, migration and invasion of non-small cell lung cancer


Autoři: Jian-Guo Zhao aff001;  Jian-Fang Wang aff001;  Jiang-Feng Feng aff001;  Xue-Ying Jin aff001;  Wan-Li Ye aff002
Působiště autorů: Department of Oncology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China aff001;  Department of Radiotherapy, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, China aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225755

Souhrn

Objective

The primary purpose of this study is to investigate the effect of hedgehog-interacting protein (HHIP) overexpression on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC).

Methods

Firstly, HHIP gene expression data of NSCLC tissues and normal tissues were obtained from GSE18842/GSE19804/GSE43458 databases of the Gene Expression Omnibus (GEO) database and then validated by TCGA NSCLC database in a cohort of 1027 cases of NSCLC patients and 108 cases of normal people. A chi-square test was used to analyze the relationship between HHIP expression and clinicopathological characteristics of NSCLC. The expression levels of HHIP in NSCLC cells were detected by quantitative-real time PCR. The function of HHIP was investigated by a series of in vitro assays. CCK-8, wounding healing, Transwell invasion assay were utilized to explore the mechanisms of HHIP.

Results

HHIP mRNA were significantly down-regulated in NSCLC in three GEO databases and TCGA database (P<0.05). This result was confirmed in NSCLC cell lines by qRT-PCR analysis, its expression in normal NSCLC cell line BEAS-2B was significantly higher than that in NSCLC cells. Chi-square test results showed that the low expression of HHIP was correlated with gender, cancer type, TNM stage and tumor size. Functional experimental results showed that over-expressing HHIP significantly decreased the ability of cell proliferation, migration and invasion in NSCLC cells (P<0.05).

Conclusion

Overall, the above results indicated that HHIP could regulate proliferation, migration and invasion, and could be used as a judging criterion for identifying NSCLC classification and stage.

Klíčová slova:

Adenocarcinoma of the lung – Cancer cell migration – Gene expression – Hedgehog signaling – Lung and intrathoracic tumors – Malignant tumors – Non-small cell lung cancer – Secondary lung tumors


Zdroje

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