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NAIF1 inhibits gastric cancer cells migration and invasion via the MAPK pathways
1Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.
Purpose:
Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood.
Methods:
The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo.
Results:
The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2.
Conclusions:
Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.
Insights
Nuclear apoptosis-inducing factor 1 (NAIF1) inhibits gastric cancer cell proliferation, migration, and invasion. NAIF1 shows potential as a therapeutic target for gastric cancer by affecting key signaling pathways.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Nuclear apoptosis-inducing factor 1 (NAIF1) expression is reduced in gastric cancer.
- The precise role of NAIF1 in gastric cancer progression remains unclear.
- NAIF1 has shown potential to induce apoptosis in gastric cancer cells.
Purpose of the Study:
- To investigate the functional role of NAIF1 in gastric cancer cells.
- To elucidate the molecular mechanisms underlying NAIF1's effects on gastric cancer.
- To evaluate NAIF1 as a potential therapeutic target for gastric cancer.
Main Methods:
- Cell viability assessed using MTT and colony formation assays.
- Cell migration and invasion analyzed via transwell assays.
- Protein and RNA expression levels determined by Western blot and qPCR, respectively.
- In vivo anti-tumor efficacy evaluated in a xenograft mouse model.
Main Results:
- NAIF1 overexpression suppressed proliferation, migration, and invasion in gastric cancer cell lines (BGC823, MKN45).
- NAIF1 reduced tumor growth in a xenograft model.
- NAIF1 downregulated MMP2, MMP9, FAK activation, JNK, and ERK1/2 expression.
- NAIF1 promoted JNK degradation via the ubiquitin-proteasome pathway.
Conclusions:
- NAIF1 regulates gastric cancer cell migration and invasion.
- NAIF1 impacts cellular processes through the MAPK signaling pathway.
- NAIF1 represents a promising therapeutic target for gastric cancer treatment.
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