Knockdown of Myoferlin Suppresses Migration and Invasion in Clear-Cell Renal-Cell Carcinoma

Abstract

Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.

Coupling of Cell Surface Biotinylation and SILAC-Based Quantitative Proteomics Identified Myoferlin as a Potential Therapeutic Target for Nasopharyngeal Carcinoma Metastasis

“…To investigate the function of MYOF in NPC metastasis, we knocked down MYOF in high metastatic 5-8F cells. Consistent with a previous study in breast cancer cells (Turtoi et al, 2013) and Clear-Cell Renal-Cell Carcinoma (Cox et al, 2020), MYOF knockdown markedly in vitro inhibit cell proliferation, migration and invasion. Indeed, previous studies demonstrated that MYOF depletion reduced tumor development in a xenograft model of human breast cancer (Turtoi et al, 2013).…”

Lysosomal retargeting of Myoferlin mitigates membrane stress to enable pancreatic cancer growth

“…Finally, high MYOF expression distinguishes a cohort of patient PDA tumours that predict worse overall survival. Several other cancers also show elevated MYOF expression [47][48][49][50] however a role for MYOF in regulation of lysosome function in these cancers remains unknown.…”

Otoferlin is a prognostic biomarker in patients with clear cell renal cell carcinoma: A systematic expression analysis

“…For instance, overexpression of myoferlin on mRNA and protein level with influence on carcinogenesis has been found in ccRCC, breast cancer, lung cancer and pancreatic adenocarcinoma. [4][5][6][7][8] The expression level of the long non-coding RNA, Fer1L4, has been reported to be either increased or decreased depending on the tumor entity due to oncogenic or suppressive properties. In ccRCC, overexpression of Fer1L4 is associated with shortened survival, whereas lower expression levels were found in gastric and colon cancer leading to poor prognosis.…”

“…In recent years, altered expression patterns of some ferlin family members have thus been found in several tumor entities. For instance, overexpression of myoferlin on mRNA and protein level with influence on carcinogenesis has been found in ccRCC, breast cancer, lung cancer and pancreatic adenocarcinoma 4–8 . The expression level of the long non‐coding RNA, Fer1L4 , has been reported to be either increased or decreased depending on the tumor entity due to oncogenic or suppressive properties.…”