MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1.
MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1.
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MicroRNA-497 通过靶向 KSR1 抑制肿瘤生长并增加对 5-氟尿嘧啶治疗的化疗敏感性
DOI：
10.18632/oncotarget.6545
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发表时间：
2016-01-19
期刊：
影响因子：
--
通讯作者：
Jiang BH
中科院分区：
文献类型：
--
作者：
Wang L;Jiang CF;Li DM;Ge X;Shi ZM;Li CY;Liu X;Yin Y;Zhen L;Liu LZ;Jiang BH
结直肠癌(CRC)是世界上主要的癌症相关死亡原因之一。最近，在结直肠癌组织中观察到microRNA-497(miR-497)的下调。在这项研究中，我们发现miR-497在人结直肠癌组织中的表达水平低于邻近正常组织。MIR-497的表达水平与临床分期和淋巴结转移密切相关。此外，已知的癌基因KSR1是miR-497的直接靶点，并且KSR1的表达水平与miR-497在结直肠癌标本中的表达水平呈负相关。过表达miR-497抑制了细胞的增殖、迁移和侵袭，并增加了对5-氟尿嘧啶的化疗敏感性，而强制表达KSR1则有相反的作用。综上所述，这些结果表明，较低水平的miR-497在人结直肠癌组织中诱导KSR1的表达，而KSR1与结直肠癌的发生、晚期、转移和化疗耐药有关。较低的miR-497水平可能是判断结直肠癌晚期和治疗反应的潜在生物标志物。
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR-497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response.