Choi Sujin, Kim Kyeongmi, Yeo Hyunjeong, Lee Gyurim, Kim Isaac, Oh Jisu, An Hyun-Ju, Lee Soonchul
Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Republic of Korea.
Department of Laboratory Medicine, CHA Ilsan Medical Center, CHA University School of Medicine, 1205, Jungang-ro, Ilsandong-gu, Goyang-si 10414, Gyeonggi-do, Republic of Korea.
Cancers (Basel). 2023 Jul 30;15(15):3888. doi: 10.3390/cancers15153888.
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.
微小RNA（miRNA）在肿瘤的发病机制和进展中作为致癌或肿瘤抑制因子发挥着关键作用。然而，很少有研究调查miR - 4284在肾细胞癌（RCC）中的具体作用。我们旨在研究miR - 4284作为肿瘤抑制因子在肾癌细胞系中的作用。用miR - 4284转染A498和Caki - 1细胞。使用细胞计数试剂盒 - 8、集落形成、凋亡检测和定量逆转录 - 聚合酶链反应来评估肿瘤生长抑制功能。进行伤口愈合、transwell和球体形成检测以研究致瘤特性。预测并通过实验验证了miR - 4284的潜在靶基因。进行异种移植实验以评估miR - 4284的肿瘤生长抑制功能。miR - 4284过表达抑制肾癌细胞的增殖、诱导凋亡并抑制其致瘤特性。谷氨酸脱羧酶1（GAD1）是miR - 4284的直接靶标。注射了转染miR - 4284的Caki - 1细胞的异种移植小鼠模型显示肿瘤生长速率和体积显著降低。miR - 4284在体外和体内影响肾癌细胞的肿瘤生长、转移和凋亡。这些发现突出了miR - 4284作为RCC中抗癌miRNA治疗靶点的潜力。
