PDLIM2 Suppression Inhibit Proliferation and Metastasis in Kidney Cancer

Abstract

Simple Summary Kidney cancer is a common malignant tumor in both men and women and accounts for approximately 5% of all cancer incidences. Advances in imaging technology and the increasing use of health care facilities have led to the early detection of kidney cancer cases. However, many individuals are still diagnosed with metastatic kidney cancer. If the cancer is accompanied by metastases at the time of diagnosis, the 5-year survival rate is 12%. Despite the beneficial effects of anticancer drug treatment on the survival of patients with metastatic kidney cancer, survival may be less than a year. PDLIM2 plays an essential role in cancer formation and inhibition. To verify oncogenic function of the PDLIM2, we conducted several experiments and animal experiments. Our findings indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer. Abstract We evaluated the expression of PDLIM2 in human kidney cancer cell lines from primary or metastatic origins and found that PDLIM2 expression was highly elevated in metastatic kidney cancers. We evaluated the effect of PDLIM2 inhibition by RNA interference method. PDLIM2 knockdown showed the decreased proliferation and metastatic character in human metastatic kidney cancer cells. By repeated round of orthotopic injection of RenCa mouse kidney cancer cell line, we obtained metastatic prone mouse kidney cancer cell lines. PDLIM2 expression was highly expressed in these metastatic prone cells comparing parental cells. In addition, we evaluated the in vivo efficacy of PDLIM2 knockout on the tumor formation and metastasis of kidney cancer cells using a PDLIM2 knockout mice. The experimental metastasis model with tail vein injection and orthotopic metastasis model injected into kidney all showed reduced lung metastasis cancer formation in PDLIM2 knockout mice comparing control Balb/c mice. Overall, our findings indicate that PDLIM2 is required for cancer formation and metastasis in metastatic kidney cancer, indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer.