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TRIM28 knockdown increases sensitivity to etoposide by upregulating E2F1 in non-small cell lung cancer
Lei Liu1, Lijun Xiao1, Xiujun Liang2
1Department of Immunology, Basic Medical Institute, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
Abstract:
Tripartite motif containing 28 (TRIM28) is a universal corepressor for Kruppel‑associated box zinc finger proteins. In our previous study, it was shown that expression of TRIM28 is upregulated in non‑small cell lung cancer (NSCLC) cell lines and tissues. Here, we demonstrated that the stable silencing of TRIM28 expression by a specific siRNA lentivirus vector increased the sensitivity of NSCLC cells to chemotherapeutic agent etoposide. Combination of TRIM28 siRNA and etoposide significantly inhibited the growth and proliferation of lung adenocarcinoma PAa cells and exerted obvious antitumor effects in nude mice. Using FCM and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay, we found that TRIM28 siRNA in combination with etoposide increased apoptosis in vitro and in vivo which was induced by E2F1 activity, since the expression of E2F1 and its target genes was significantly increased in the cotreatment group. Cell proliferation and apoptosis were almost completely abolished in the PAa cells cotreated with TRIM28 siRNA and etoposide following knockdown of E2F1. The results of our study demonstrated that the combination of TRIM28 siRNA and etoposide may be effective against NSCLC and has the potential of being a new therapeutic tool for future treatment.
Insights
Silencing Tripartite Motif Containing 28 (TRIM28) enhances non-small cell lung cancer (NSCLC) cell sensitivity to etoposide. This combination therapy, involving TRIM28 siRNA and etoposide, shows significant antitumor effects by increasing apoptosis via E2F1 activity.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tripartite Motif Containing 28 (TRIM28) is a corepressor upregulated in non-small cell lung cancer (NSCLC).
- Previous studies indicated TRIM28's role in NSCLC progression.
Purpose of the Study:
- To investigate the therapeutic potential of silencing TRIM28 in combination with etoposide for NSCLC treatment.
- To elucidate the mechanism underlying the combined effect of TRIM28 silencing and etoposide on NSCLC cells.
Main Methods:
- Stable silencing of TRIM28 using siRNA lentivirus vector in NSCLC cells.
- Assessment of cell sensitivity to etoposide, cell growth, proliferation, and apoptosis (in vitro and in vivo).
- Flow cytometry (FCM) and TUNEL assay were used to measure apoptosis; E2F1 activity and target gene expression were analyzed.
Main Results:
- TRIM28 silencing increased NSCLC cell sensitivity to etoposide.
- Combination therapy significantly inhibited NSCLC cell growth and proliferation in vitro and showed antitumor effects in vivo.
- TRIM28 siRNA and etoposide cotreatment enhanced apoptosis, mediated by increased E2F1 activity and its target genes.
Conclusions:
- Combined TRIM28 siRNA and etoposide demonstrate significant antitumor effects in NSCLC.
- This combination therapy, acting through E2F1, represents a potential novel therapeutic strategy for NSCLC.
