Abstract
Myoferlin (MYOF) has emerged as an oncogenic protein in various human cancer types. This study was conducted to investigate comprehensively the expression and functional properties of MYOF in clear-cell renal-cell carcinoma (ccRCC) with respect to its value as diagnostic biomarker and therapeutic target. mRNA and protein expression of MYOF were assessed by quantitative polymerase chain reaction and immunohistochemistry. siRNA-mediated knockdown of MYOF was performed in the RCC cell line ACHN followed by proliferation, migration and invasion assays. MYOF mRNA and protein expression were significantly up-regulated in ccRCC. Higher mRNA levels were measured in advanced tumors. MYOF protein expression was increased in tumors with higher histological grades, and those with positive lymph node and surgical margin status. MYOF knockdown led to reduction of migration and invasion in ACHN cells, whereas expression of angiogenesis-associated genes tyrosine-protein kinase receptor-2 (TIE2), angiopoietin 2 (ANG2) and caveolin-1 (CAV1) was up-regulated following knockdown. MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.
Highlights
Renal cell carcinoma (RCC) is the most frequent solid renal malignancy and represents 2-3% of all cancer cases worldwide
Mutations of the other ferlins such as myoferlin (MYOF; formerly FER1L3), FER1L4, FER1L5 and FER1L6 have not been associated with any distinct disease but their expression seems to play an important role in carcinogenesis
In the The Cancer Genome Atlas (TCGA) cohort, significantly higher levels of MYOF mRNA expression were found in Clear cell RCC (ccRCC) tumor tissues compared to benign samples (p
Summary
Renal cell carcinoma (RCC) is the most frequent solid renal malignancy and represents 2-3% of all cancer cases worldwide. Implementation of tyrosine kinase receptor inhibitors or mechanistic target of rapamycin inhibitors has achieved improvement in therapy of metastatic RCC. It is important to identify novel biomarkers as progression or predictive factors, especially with regard to targeted therapy. Mutations of the other ferlins such as myoferlin (MYOF; formerly FER1L3), FER1L4, FER1L5 and FER1L6 have not been associated with any distinct disease but their expression seems to play an important role in carcinogenesis. MYOF has emerging oncogenic impact and promotes cancer cell proliferation via different molecular mechanisms. Little is known about the functional role of MYOF in ccRCC. We investigated its expression and functional properties in ccRCC cells to identify its value as a diagnostic biomarker and therapeutic target
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