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. 2022 Apr;13(4):10324-10334.
doi: 10.1080/21655979.2022.2063561.

Heat shock factor 2-binding protein promotes tumor progression via activation of MAPK signaling pathway in lung adenocarcinoma

Junyuan Liu  1 , Yuting Zhang  2 , Jie Tao  1 , Tingting Yu  1 , Tao Zhang  3
Affiliations

Heat shock factor 2-binding protein promotes tumor progression via activation of MAPK signaling pathway in lung adenocarcinoma

Junyuan Liu et al. Bioengineered. 2022 Apr.

Abstract

Lung adenocarcinoma (LUAD) is a malignant tumor that causes a serious public health burden. The biological functions and potential mechanism of heat shock factor 2-binding protein (HSF2BP) in LUAD have not been studied. This study aimed to explore the HSF2BP expression pattern and its potential biological function in LUAD. The transcriptome data and relevant clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. The mRNA levels and prognosis of HSF2BP were determined using TCGA datasets. The protein and mRNA expression levels of HSF2BP were identified by conducting western blot analysis and quantitative real-time polymerase chain reaction in tissues and cells, respectively. To determine whether HSF2BP affected the biological function of LUAD cell lines, a series of functional experiments were performed in vitro and in vivo. In addition, gene set enrichment analysis was applied to determine the pathways that HSF2BP regulated, which was further confirmed by western blotting, and the high expression of HSF2BP was observed in LUAD, which was correlated with the unfavorable prognosis in LUAD patients. Clinical correlation analysis revealed that tumor stage was positively correlated with high HSF2BP expression. Furthermore, HSF2BP could serve as an independent risk factor for overall survival. In vitro, HSF2BP knockdown suppressed the proliferation and migration of A549 and H1299 cells. We observed the same results in vivo experiments. Mechanistically, the HSF2BP regulates the mitogen-activated protein kinase signaling pathway to perform its biological function. The HSF2BP plays a role in the development of LUAD and could be a useful anticancer target for the treatment of LUAD.

Keywords: HSF2BP; MAPK signaling pathway; lung adenocarcinoma; prognosis.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
HSF2BP expression and prognosis in LUAD based on TCGA datasets. (a) The mRNA expression in LUAD and normal samples. (b) The expression in LUAD and paired normal samples. (c) Correlation analysis between HSF2BP expression and tumor stage. (d) Survival curves of HSF2BP in LUAD. (e) Cox regression analysis of HSF2BP and clinical parameters.
Figure 2.
Figure 2.
The expression of HSF2BP in LUAD tissues and cells. (a-b) The mRNA expression of HSF2BP in LUAD and normal tissues. (c) The protein expression of HSF2BP in LUAD and adjacent tissues which was detected by western blot. (d) The protein expression of HSF2BP in LUAD and adjacent tissues which was detected by IHC. (e) The protein expression of HSF2BP in LUAD cell lines and BEAS-2B. Note: * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 3.
Figure 3.
HSF2BP promotes the proliferation and migration of LUAD cells. (a) The transfection efficacy of lentivirus down-regulating HSF2BP in A549 and NCI-H209 cells. (b) The cell viability of A549 and NCI-H209 cells were determined by CCK-8 assay. (c) The colony formation assay was used to measure proliferation in LUAD cells. (d) Wound healing assay in A549 and NCI-H209 cells. (e) Transwell assay was used to determine the migration ability of LUAD cells. Note: * p > 0.05, ** p < 0.01, *** p < 0.001.
Figure 4.
Figure 4.
HSF2BP is involved in the regulation of MAPK signaling pathway. (a) GSEA analysis of HSF2BP. (b) The expression level of p-ERK, total ERK, p-JNK, total JNK, p-p38 and total p38 in LUAD cells by western blot.
Figure 5.
Figure 5.
HSF2BP promotes the tumor growth in vivo. (a) The tumor formed by shCtrl and sh-HSF2BP cells. (b) Tumor volume. (c) Tumor weight. (d) HE staining. (e) Ki67 expression detected by immunohistochemistry. Note: * p < 0.001.
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