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Introduction: Calpain small subunit 1 (Capns1) has shown its correlation with the metastasis and invasion of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the expression and function of Capns1 in human renal cell carcinoma (RCC) have not been clarified. This study aimed to examine the expression of Capns1 in RCC tissues and cell lines and to assess its role performed in RCC., Methods: Capns1 expression was evaluated in 75 pairs of RCC and matched adjacent non-tumor tissues by immunohistochemistry. The prognostic value of Capns1 in RCC was assessed by Kaplan-Meier and Cox regression analyses. The action of Capns1 in the proliferation, adhesion, migration, and invasion of RCC cells and the effects on matrix metalloproteinase (MMP) 2 and 9 expression were evaluated after Capns1 silence., Results: Capns1 expression was significantly higher in RCC tissues compared with the adjacent non-tumor tissues. Multivariate analysis showed that Capns1 overexpression was an independent poor prognostic marker in RCC. The silencing of Capns1 prohibited cell adhesion and impaired the migration and invasion ability of 786-O cells in vitro. Furthermore, Capns1 silence reduced MMP2 and MMP9 expression., Conclusion: Capns1 overexpression predicts poor prognosis and correlates with tumor progression in RCC. Capns1 expression might serve a prognostic marker and therapeutic target for RCC., (© 2021 S. Karger AG, Basel.)

Calpain small subunit 1 (Capn4) has been shown to correlate with the metastasis/invasion of clear cell renal cell carcinoma (ccRCC). This study aimed to further elucidate the molecular mechanisms underlying Capn4-mediated ccRCC progression. The mRNA expression levels in ccRCC cells were measured by quantitative real-time PCR. The effects of Capn4 on cell adhesion, invasion, and migration were examined by cell adhesion assay, cell invasion assay, and wound-healing assay, respectively. The protein levels were detected by western blot analysis. The effect of Capn4 on cancer metastasis in vivo was assessed in a nude mice xenograft model. It was found that Capn4 was up-regulated in the ccRCC cells, and Capn4 overexpression suppressed cell adhesion activity and increased cell invasion and migration in 786-O cells, while Capn4 silencing increased cell adhesion activity and impaired the invasion and migration ability of Caki-1 cells. Capn4 overexpression also increased the protein level of cleaved talin in 786-O cells, while Capn4 silencing decreased the protein level of cleaved talin in Caki-1 cells. The focal adhesion kinase (FAK)/AKT/MAPK signaling was activated by Capn4 overexpression in 786-O cells, and was inhibited by Capn4 down-regulation in Caki-1 cells. Capn4 overexpression increased the protein levels of matrix metalloproteinase 2 (MMP-2), vimentin, N-cadherin, and down-regulated E-cadherin in 786-O cells, while Capn4 silencing decreased the protein levels of MMP-2, vimentin, N-cadherin, and up-regulated E-cadherin in Caki-1 cells. Capn4 also promoted cancer metastasis in the in vivo nude mice xenograft model. Our results implicate the functional role of Capn4 in ccRCC invasion and migration, which may contribute to cancer metastasis in ccRCC.

Objective: Renal cancer accounts for about 3% of human cancer, and clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Recently, microRNAs (miRNAs) are found to be the biomarkers for cancer diagnosis, prognosis and the targets for tumor management. This study aimed to examine the expression of miR-337-3p in ccRCC and to elucidate the molecular mechanisms underlying miR-337-3p-mediated ccRCC progression., Methods: The miRNA and mRNA expression levels in ccRCC cells and tissues were measured by qRT-PCR. Cell proliferation, cell adhesion, colony growth and cell invasion were examined by CCK-8 assay, cell adhesion assay, colony formation assay and Transwell invasion assay, respectively. The protein levels were detected by western blot assay. The effects of miR-337-3p on tumor growth in vivo was assessed in a nude mice xenograft model., Results: MiR-337-3p was down-regulated in ccRCC cell lines, and miR-337-3p overexpression suppressed cell proliferation, colony growth and invasion, but enhanced cell adhesion in ccRCC; while knockdown of miR-337-3p exerted the opposite effects on ccRCC. Bioinformatics analysis and luciferase reporter assay showed that Calpain small subunit 1 (Capn4) was negatively regulated by miR-337-3p, and overexpression of miR-337-3p attenuated the miR-337-3p-mediated effects on ccRCC cellular functions. In addition, miR-337-3p also suppressed epithelial-mesenchymal transition in ccRCC. The in vivo tumor growth was markedly suppressed after miR-337-3p overexpression. Data from clinical data showed that down-regulation of miR-337-3p and up-regulation of Capn4 mRNA and protein were identified in the ccRCC tissues, and miR-337-3p expression level was inversely correlated with Capn4 mRNA expression level in ccRCC tissues., Conclusions: Collectively, these data suggested the tumor suppressive role of miR-337-3p in ccRCC. MiR-337-3p suppressed cell proliferation and metastasis in ccRCC partially via targeting Capn4.

Objective: To investigate the mRNA and protein levels of calpain small subunit-1 (Capn4) in human clear cell renal cell carcinoma (ccRCC), to analyse the relationship between Capn4 mRNA level and pathological stage of ccRCC, and to examine the potential of Capn4 as a prognostic factor in ccRCC., Methods: mRNA and protein levels of Capn4 were measured in pairs of tumour tissues and matched adjacent nontumour tissue obtained from patients with ccRCC by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Associations of the mRNA level of Capn4 with pathological tumour stage and the overall survival of ccRCC patients were also analysed., Results: Capn4 mRNA and protein level were significantly higher in ccRCC tumour tissues compared with adjacent nontumour tissues as assessed by qRT-PCR and Western blotting, respectively. Higher Capn4 mRNA levels were observed in patients with more advanced pathological stage of ccRCC and were also associated with decreased overall survival of patients with ccRCC., Conclusions: The findings from this study indicate that Capn4 has the potential to be an independent prognostic indicator for ccRCC.