HSPB8 promotes cancer cell growth by activating the ERK‑CREB pathway and is indicative of a poor prognosis in gastric cancer patients

Abstract

Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide, especially in East Asia. Discovery of new biomarker and the elucidation of the molecular mechanisms involved in GC development and progression continue to be important issues for both researchers and clinicians. In the present study, we report that siRNA knockdown of heat shock protein family B (small) member 8 (HSPB8) inhibited the proliferation of GC cells and promoted their apoptosis. Analysis of TCGA dataset indicated that the HSPB8 expression level was strongly positively correlated with the KEGG MAPK signaling pathway (P<0.001, FDR=0.006) and BIOCARTA CREB pathway (P=0.006, FDR=0.043). The association between HSPB8 and the ERK‑CREB pathway was confirmed by western blot analysis and we found that pERK and pCREB were significantly decreased following HSPB8 knockdown. Downstream genes of the ERK‑CREB pathway were all significantly decreased following HSPB8 knockdown. By evaluating the survival of TCGA GC patients, we found that patients with a high HSPB8 level exhibited significantly worse prognosis than those with low HSPB8 in both overall survival (OS) (log‑rank χ2=10.60, P=0.001) and disease‑free survival (DFS) (log‑rank χ2=11.31, P<0.001). The methylation level of HSPB8 DNA was significantly negatively associated with its expression (R=‑0.1368, P=0.041), and positively associated with OS (log‑rank χ2=10.60, P=0.001). In conclusion, we provide evidence that HSPB8 promotes cancer cell growth by activating the ERK‑CREB pathway and may serve as a potential prognostic factor in GC patients.

Development of prognostic index based on autophagy-related genes analysis in breast cancer

“…Overexpression of EIF4G1 is associated with tumor progression and poor prognosis in nasopharyngeal carcinoma [14]. HSPB8 promotes cancer cell growth and is associated with poor prognosis in patients with gastric cancer [15]. Overexpression of phosphorylated EIF4EBP1 is closely associated with tumor recurrence and worse survival outcomes of cervical cancer [16].…”

<p>Competing Endogenous RNA (ceRNA) Network Analysis of Autophagy-Related Genes in Hepatocellular Carcinoma</p>

“… 48 – 50 HSPB8 could also be involved in the development and migration of cancer in a non-autophagy dependent form. 51 , 52 …”

“…[48][49][50] HSPB8 could also be involved in the development and migration of cancer in a non-autophagy dependent form. 51,52 All of the three genes seem to have two-sided effects, promoting and inhibiting cancer. It is more interesting and significant to study the role of a cluster of ATGs involved in cancer than a single gene.…”

Autophagy-related genes are potential diagnostic and prognostic biomarkers in prostate cancer

“…Heat shock protein B8 (HSPB8) is a member of common small heart shock protein family. Shen et al (29) found that HSPB8 promoted cell growth and was related to a poor prognosis in patients with gastric cancer. NK2 homeobox 3 (NKX2-3) is located on 10q24.2 and encodes homeodomain-containing transcription factor.…”