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Published on: March 12, 2018
The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma
Jian-Yu Zhang1, Ke-Zhi Shi1, Xiang-Yu Liao1
1The First College of Clinical Medical Science, Three Gorges University & Yichang Central People's Hospital, Yichang, China.
Abstract:
The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.
Insights
The proteasome subunit PSMC6 is highly expressed in lung adenocarcinoma (LUAD), correlating with poor prognosis. Inhibiting PSMC6 suppressed LUAD cell growth, indicating its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The proteasome is a validated anticancer target.
- The specific role of proteasome subunit PSMC6 in lung adenocarcinoma (LUAD) remains unclear.
Purpose of the Study:
- To investigate the expression, prognostic value, and molecular mechanism of PSMC6 in LUAD.
- To evaluate PSMC6 as a potential therapeutic target for LUAD.
Main Methods:
- Quantitative analysis of PSMC6 RNA and protein expression in LUAD tissues.
- Correlation analysis between PSMC6 expression and clinical/pathological features.
- Functional studies using small interference RNAs (siRNAs) to silence PSMC6 in LUAD cell lines.
- Gene set enrichment analysis (GSEA) to explore molecular pathways.
Main Results:
- PSMC6 RNA and protein were significantly upregulated in LUAD tissues compared to normal tissues.
- High PSMC6 expression was associated with poor prognosis and poor tumor differentiation.
- PSMC6 silencing inhibited LUAD cell proliferation, migration, and invasion.
- PSMC6 expression positively correlated with other proteasome subunits involved in AXIN protein degradation.
- PSMC6 overexpression was linked to WNT signaling pathway activation.
Conclusions:
- PSMC6 is overexpressed in LUAD and serves as a negative prognostic biomarker.
- PSMC6 promotes LUAD progression by potentially activating WNT signaling through AXIN protein degradation.
- PSMC6 represents a promising therapeutic target for lung adenocarcinoma.
