Zhang Shoulin, Zhang Dongmei, Yi Chunguang, Wang Yinping, Wang Hongan, Wang Jian
Internal Medicine Department, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Scientific Research Office, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2016 Jan;35(1):559-67. doi: 10.3892/or.2015.4333. Epub 2015 Oct 16.
Accumulating evidence demonstrates that microRNA-22 (miR-22) was deregulated in many types of cancers and was involved in various cellular processes related to carcinogenesis. However, the exact roles and mechanisms of miR-22 remain unknown in human renal cell carcinoma (RCC). Here, the relationship between miR-22 expression pattern and clinicopathological features of patients with EOC were determined by real-time quantitative RT-PCR (qRT-PCR). Furthermore, the role of miR-22 and possible molecular mechanisms in EOC were investigated by several in vitro approaches and in a nude mouse model. Results from qRT-PCR showed that miR-22 was significantly downregulated in RCC samples compared with corresponding non-cancerous tissues, which was significantly associated with tumor stage and lymph node metastasis. Functional study demonstrated that enforced overexpression of miR-22 in renal cancer cells inhibited proliferation, migration and invasion, and induced cell apoptosis in vitro, and suppressed tumor growth in vivo. In addition, SIRT1 was identified as a direct target of miR-22 by a luciferase reporter assay. Overexpression of miR-22 activated p53 and its downstream target p21 and PUMA, and the apoptosis markers cleaved CASP3 and PARP, and inhibited epithelial-mesenchymal transition (EMT). These findings showed that miR-22 functioned as tumor suppressor in RCC and blocked RCC growth and metastasis by directly targeting SIRT1 in RCC, indicating a potential novel therapeutic role in RCC treatment.
越来越多的证据表明，微小RNA-22（miR-22）在多种癌症中表达失调，并参与了与癌症发生相关的各种细胞过程。然而，miR-22在人类肾细胞癌（RCC）中的具体作用和机制仍不清楚。在此，通过实时定量逆转录PCR（qRT-PCR）确定了miR-22表达模式与上皮性卵巢癌（EOC）患者临床病理特征之间的关系。此外，通过多种体外实验方法和裸鼠模型研究了miR-22在EOC中的作用及可能的分子机制。qRT-PCR结果显示，与相应的癌旁组织相比，RCC样本中miR-22显著下调，这与肿瘤分期和淋巴结转移显著相关。功能研究表明，在肾癌细胞中强制过表达miR-22可抑制体外增殖、迁移和侵袭，并诱导细胞凋亡，在体内可抑制肿瘤生长。此外，通过荧光素酶报告基因实验确定SIRT1是miR-22的直接靶点。miR-22的过表达激活了p53及其下游靶点p21和PUMA，以及凋亡标志物裂解的CASP3和PARP，并抑制上皮-间质转化（EMT）。这些发现表明，miR-22在RCC中发挥肿瘤抑制作用，并通过直接靶向RCC中的SIRT1来阻断RCC的生长和转移，这表明其在RCC治疗中具有潜在的新治疗作用。
