PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer
Zhengbin Chai1, Li Wang2, Yabing Zheng3
1Department of Laboratory Medicine, Jinan Infectious Disease Hospital, Jingshi Road 22029, Jinan, 250021 Shandong People's Republic of China.
Background:
CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research.
Methods:
Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo.
Results:
CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells.
Conclusions:
PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.
Insights
PADI3 inhibits colon cancer growth by reducing Hsp90 and CKS1 expression. This study clarifies the upstream regulation of CKS1, offering new insights into colon cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- CKS1 is highly expressed in colon cancer and drives proliferation.
- The upstream regulation of CKS1 in colon cancer remains largely unknown.
- PADI3 has known anti-tumor roles by suppressing cell proliferation.
Purpose of the Study:
- Investigate the regulatory mechanism of PADI3 and CKS1 in colon cancer.
- Determine the relationship between PADI3 and CKS1 expression in colon cancer.
- Elucidate how PADI3 influences CKS1-driven cancer cell proliferation.
Main Methods:
- Gene expression analysis (Western blot, real-time PCR).
- Cell proliferation and colony formation assays (CCK-8, colony formation assays).
- In vivo tumor growth studies in BALB/c nude mice.
Main Results:
- CKS1 overexpression promotes colon cancer cell proliferation and tumor growth.
- PADI3 and CKS1 expression are negatively correlated in clinical colon cancer samples.
- PADI3 downregulates CKS1 expression, an effect dependent on Hsp90.
Conclusions:
- PADI3 exerts antitumor activity by inhibiting Hsp90 and CKS1.
- Hsp90 is crucial for PADI3-mediated suppression of CKS1 expression.
- Understanding this PADI3-Hsp90-CKS1 axis offers therapeutic targets for colon cancer.
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