miR-298促进肺腺癌转移及其分子机制研究

miR-298 is deregulated in a variety of cancer types, and closely related with the prognosis, while the mechanism has not been eludicated yet. We found that miR-298 is regulated by mTOR signaling in lung adenocarcinoma cell and miR-298 over expression would promote cell migration and invasion. Those results sugest that miR-298 can promote lung cancer metastasis. In this project, the function and the mechanism of miR-298 in lung cancer metastasis will be studied in tumour cell, animal model and clinical specimens. Putative targets of miR-298 will be found. Lung cancer is the most lethal cancer in China. This study would provide a new experimental evidence for clarifying the actions and mechanisms of lung cancer metastasis. An effective way to detect lung cancer metastasis may be find, and new targets for the treatment of lung adenocarcinoma may be disclosed.

miR-298在多种癌症中表达异常，并与预后密切相关，但其机制远未阐明。本课题组的前期研究表明，在肺腺癌细胞中miR-298受到mTOR信号通路的调节，过表达miR-298能够促进肺腺癌细胞的迁移和侵袭能力，这些结果提示：miR-298能够促进肺癌转移。本课题将在细胞、动物模型和肺癌临床标本中研究miR-298在肺癌转移中所发挥的作用，并找出miR-298的功能靶点，阐明其分子机制。肺癌是我国致死人数最多的恶性肿瘤，本研究将为阐明肺癌转移发生的分子机制，更好地理解肺癌这种复杂的肿瘤的生物学行为，以及肺腺癌的诊断和治疗提供新的依据。

近年来的研究表明miRNA在肿瘤转移过程中发挥重要作用，为肿瘤的诊疗和治疗提供了新思路。miR-298在多种肿瘤中表达异常，并与肿瘤预后等临床指标密切相关。本项目研究了 miR-298在肺腺癌转移中的作用及其机制。我们发现 miR-298 被mTOR信号调节，并能促进肺腺癌细胞的侵袭迁移，导致肿瘤转移。通过机制研究，我们发现miR-298被mTOR信号激活，并可被尼古丁激活。miR-298通过靶向NAA60和SAMD4B来促进肺腺癌的转移。此外，我们还研究了miR-218 在宫颈癌中的作用，我们发现miR-218与病人的临床指标相关，miR-218 能够抑制肿瘤细胞的EMT，抑制肿瘤细胞的侵袭迁移，而这一作用是通过调节其靶基因SFMFBT1和DCUN1D1。肿瘤转移是导致肿瘤病人死亡的最重要原因，我们的研究发现miR-298 和miR-218是调控肿瘤转移的重要分子，这为肿瘤的诊断和治疗提供了新的实验证据和思路。