miR-4284 Functions as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting Glutamate Decarboxylase 1.
Sujin ChoiKyeongmi KimHyunjeong YeoGyurim LeeIsaac KimJisu OhHyun Ju AnSoonchul LeePublished in: Cancers (2023)
MicroRNAs (miRNAs) play a crucial role as oncogenic or tumor suppressors in the pathogenesis and progression of tumors. However, few studies have investigated the exact role of miR-4284 in renal cell carcinoma (RCC). We aimed to investigate the role of miR-4284 as a tumor suppressor in renal cancer cell lines. A498 and Caki-1 were transfected with miR-4284. The Cell Counting Kit-8, colony formation, apoptosis assays, and quantitative reverse transcription-polymerase chain reaction were used to evaluate tumor growth-inhibiting functions. The wound-healing, transwell, and sphere-formation assays were conducted to investigate tumorigenic characteristics. The potential target genes of miR-4284 were predicted and experimentally verified. A xenograft experiment was performed to estimate the tumor-growth-suppressive function of miR-4284. miR-4284 overexpression suppressed proliferation, induced apoptosis, and suppressed tumorigenic features of renal cancer cells. Glutamate decarboxylase 1 (GAD1) was directly targeted by miR-4284. A xenograft mouse model injected with Caki-1 cells transfected with miR-4284 showed significantly decreased tumor growth rate and volume. miR-4284 affected tumor growth, metastasis, and apoptosis of renal cancer cells in vitro and in vivo. These findings highlight the potential of miR-4284 as a target for anticancer miRNA therapeutics in RCC.
Keyphrases
- cell proliferation
- long non coding rna
- long noncoding rna
- induced apoptosis
- renal cell carcinoma
- endoplasmic reticulum stress
- oxidative stress
- mouse model
- signaling pathway
- squamous cell carcinoma
- transcription factor
- drug delivery
- genome wide
- mesenchymal stem cells
- climate change
- risk assessment
- wound healing
- human health
- high resolution
- single molecule
- high speed
- atomic force microscopy