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在透明细胞肾细胞癌中,微小RNA-223-3p通过下调溶质载体家族4成员4促进细胞增殖和转移。

MiR-223-3p promotes cell proliferation and metastasis by downregulating SLC4A4 in clear cell renal cell carcinoma.

作者信息

Xiao Wen, Wang Xuegang, Wang Tao, Xing Jinchun

机构信息

Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

Center of Diagnosis and Treatment of Urinary System Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

出版信息

Aging (Albany NY). 2019 Jan 22;11(2):615-633. doi: 10.18632/aging.101763.

Abstract

MicroRNAs (miRNAs) are known to affect the occurrence and progression of cancer. We therefore evaluated the involvement of miR-223-3p in renal cell cancer. MiR-223-3p was highly expressed in clear cell renal cell cancer tissues. Clear cell renal cell cancer patients with higher miR-223-3p expression had higher tumor stages and grades and poorer prognoses. In renal cancer cells, overexpression of miR-223-3p enhanced cell proliferation and metastasis, while inhibition of miR-223-3p reduced the malignant capacity of the cells. MiR-223-3p was found to bind directly to solute carrier family 4, member 4 () mRNA, thereby reducing SLC4A4 mRNA and protein expression. SLC4A4 overexpression restrained cell proliferation and metastasis by suppressing Kirsten rat sarcoma viral oncogene (KRAS) expression in renal cancer cells. expression correlated negatively with miR-223-3p expression in patient samples. Given that miR-223-3p suppressed the SLC4A4/KRAS axis, miR-223-3p gene therapy could be an effective treatment for renal cancer.

摘要

已知微小RNA(miRNA)会影响癌症的发生和发展。因此,我们评估了miR-223-3p在肾细胞癌中的作用。miR-223-3p在透明细胞肾细胞癌组织中高表达。miR-223-3p表达较高的透明细胞肾细胞癌患者具有更高的肿瘤分期和分级,预后较差。在肾癌细胞中,miR-223-3p的过表达增强了细胞增殖和转移能力,而抑制miR-223-3p则降低了细胞的恶性能力。发现miR-223-3p直接与溶质载体家族4成员4(SLC4A4)mRNA结合,从而降低SLC4A4 mRNA和蛋白表达。SLC4A4的过表达通过抑制肾癌细胞中 Kirsten 大鼠肉瘤病毒癌基因(KRAS)的表达来抑制细胞增殖和转移。在患者样本中,SLC4A4表达与miR-223-3p表达呈负相关。鉴于miR-223-3p抑制了SLC4A4/KRAS轴,miR-223-3p基因治疗可能是一种有效的肾癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3691/6366987/1f15cc2e64fe/aging-11-101763-g001.jpg

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