Oncogene文章:microRNA-133b是宮頸癌發(fā)生與發(fā)展的關鍵因素
宮頸癌(cervical carcinoma)是女性第二大惡性腫瘤,并且在年輕女性中發(fā)病率高。2002年全世界的新發(fā)病例為50萬人,死亡病例為27萬人。根據(jù)中國疾病預防與控制中心公布的數(shù)據(jù),我國每年宮頸癌新發(fā)病例為13.15 萬人,約占世界總數(shù)的26%,死亡病例為5.3 萬人,約占世界總數(shù)的20%。因此,我國的宮頸癌防治形勢非常嚴峻。
在99.8%的宮頸癌患者中均可檢測到HPV感染。但單獨的HPV 感染不足以引起宮頸癌,細胞本身必須發(fā)生相應的變化,才能最終引起宮頸癌。清華大學的程京教授與新疆醫(yī)科大學第一附屬醫(yī)院的溫浩教授合作,利用生物芯片平臺研究了宮頸癌組織中microRNA的表達變化,發(fā)現(xiàn)了20種microRNA在宮頸癌的發(fā)生和發(fā)展過程中表達量發(fā)生了改變。其中microRNA-133b在從宮頸上皮內(nèi)瘤樣病變到侵潤癌的發(fā)展過程中,表達量逐步升高。功能學實驗結(jié)果表明,這一microRNA具有促進宮頸癌發(fā)生和發(fā)展的作用。該microRNA有可能作為臨床早期診斷的新型宮頸癌標志物。
上述研究成果已申請專利,研究論文已在Oncogene雜志網(wǎng)站在線發(fā)表。其中的博奧生物晶芯®哺乳動物miRNA芯片服務與Real time RT-PCR服務在博奧生物有限公司完成。
原文摘要:
MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways
We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogenactivated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma.
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