MOB1 Inhibits Malignant Progression of Colorectal Cancer by Targeting PAK2
Jie Liu1, Zhitao Shi2, Yunyun Ma1
1Department of Proctology, Affiliated Traditional Chinese Medicine Hospital, Xinjiang Medical University, Urumqi, People's Republic of China.
Objective:
We aimed at studying the mechanism of MOB1 inhibiting the proliferation and metastasis of colorectal cancer (CRC), to provide a new guidance for the early diagnosis and treatment of CRC.
Methods:
MOB1 expression level in 68 pairs of CRC tissues and adjacent ones was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the associations between the expression level of MOB1 and the clinicopathological indicators as well as the prognosis of CRC patients were analyzed. After constructing CRC cell lines that stably overexpressing or silencing MOB1, the changes of cell proliferation and metastasis ability were examined by Cell Counting Kit (CCK-8) and Transwell assay. In addition, the interaction between MOB1 and PAK2 and how the these two genes affect the biological functions of CRC cell lines were investigated by luciferase assay, qRT-PCR and Western Blot experiments.
Results:
Our data showed that MOB1 expression level in CRC tissues was remarkably lower than that in adjacent ones. In comparison to patients of the group of high MOB1 expression, these patients of low MOB1 expression group showed higher incidence of distant or lymph node metastasis and lower survival rate. Cell functional experiments revealed that overexpression of MOB1 markedly attenuated the proliferation and migration ability of CRC cell lines compared to the NC group; In contrast, knockdown of MOB1 enhanced the above-mentioned cell abilities compared to anti-NC group. Luciferase assay verified an interaction between MOB1 and PAK2; and Western blot analysis showed a negative correlation between the expression of the MOB1 and PAK2 protein levels in CRC tissues. Subsequently, we demonstrated that MOB1 interacted with PAK2 to regulate its expression and affected the proliferation and migration capacity of CRC cell lines in vitro.
Conclusion:
In summary, the lowly expressed MOB1 in CRC tissues and cell lines may accelerate the proliferation and migration through modulating PAK2 expression.
Insights
Low MOB1 expression in colorectal cancer (CRC) accelerates tumor growth and metastasis by modulating PAK2. This finding offers new insights for CRC diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) remains a significant global health challenge.
- Understanding the molecular mechanisms underlying CRC proliferation and metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of MOB1 in inhibiting colorectal cancer (CRC) proliferation and metastasis.
- To elucidate the mechanism by which MOB1 affects CRC progression.
- To provide guidance for the early diagnosis and treatment of CRC.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess MOB1 expression in CRC tissues.
- Cell Counting Kit (CCK-8) and Transwell assays to evaluate cell proliferation and migration.
- Luciferase assay, qRT-PCR, and Western Blot to investigate the interaction between MOB1 and PAK2.
Main Results:
- MOB1 expression was significantly lower in CRC tissues compared to adjacent tissues.
- Low MOB1 expression correlated with increased metastasis and poorer prognosis in CRC patients.
- Overexpression of MOB1 inhibited CRC cell proliferation and migration, while MOB1 knockdown enhanced these processes.
- MOB1 was found to interact with PAK2, negatively regulating its expression and affecting CRC cell behavior.
Conclusions:
- Reduced MOB1 expression in colorectal cancer promotes tumor proliferation and migration.
- The mechanism involves MOB1 modulating PAK2 expression.
- These findings highlight MOB1 as a potential therapeutic target and biomarker for CRC.
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