Abstract
Clear cell renal cell carcinoma (ccRCC) exhibits the highest mortality among all urological malignancies. The investigation of the potential disease progression markers can improve ccRCC diagnosis and treatment. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is involved in carcinogenesis and cancer progression in a variety of cancer types including RCC. While, its role in ccRCC remains unclear, this cancer type is considered the most aggressive RCC subtype. In the present study, RT-qPCR, western blotting and immunohistochemical (IHC) assays demonstrated that GRIM-19 protein and mRNA levels were downregulated in ccRCC tumor tissues compared with the corresponding levels noted in paracancerous non-tumor tissues. The deficiency of this protein contributed in relaxed and/or collapsed structures of the kidney tubules and collecting duct noted in tumor tissues. Moreover, the reduction in GRIM-19 expression was associated with high tumor, lymph nodes and metastasis (TNM) stage and Fuhrman grade of ccRCC tumors. The data suggested that GRIM-19 acted as a tumor suppressor and that its deficiency promoted ccRCC development and progression. GRIM-19 can be considered a potential tumor marker for ccRCC.
Highlights
Renal cell carcinoma (RCC) accounts for approximately 3% of all human malignancies and approximately 85% of renalKey words: gene associated with retinoid‐interferon‐induced mortality‐19, clear cell renal cell carcinoma, development, progression cancer [1]
Gene associated with retinoid‐interferon‐induced mortality‐19 (GRIM‐19) mRNA downregulation is associated with Clear cell renal cell carcinoma (ccRCC) clinical progression
GRIM‐19 is commonly regarded as a tumor suppressor in certain cancer types
Summary
Renal cell carcinoma (RCC) accounts for approximately 3% of all human malignancies and approximately 85% of renal. Gene associated with retinoid‐interferon‐induced mortality‐19 (GRIM‐19) is a member of the GRIM family of proteins [7,8]. It is essential for the tumor cell death induced by interferon‐β and retinoic acid. GRIM‐19 is well‐known as a cell death regulatory gene widely distributed in the cytoplasm, nucleus and mitochondria and has been studied as a suppressor of various types of cancer [11,12,13,14,15,16,17]. The present study analyzed the mRNA and protein expression levels and distribution of GRIM‐19 in ccRCC tumor tissues compared with those noted in the paracancerous non‐tumor tissues, and demonstrated that GRIM‐19 deficiency promoted ccRCC malignant progression by causing an increase in the tumor, lymph nodes and metastasis (TNM) stage and the Fuhrman grade of the tumors
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