LncRNA-MNX1-AS1促进胆囊癌增殖转移的机制及其潜在诊断治疗价值

Gallbladder cancer, the most common cancer of the biliary tract, has an extremely poor prognosis. Meanwhile, its scientific research has got less attention than other types of malignancies. As a result, no effect adjuvant therapy has been applied clinically. Therefore, it is meaningful to conduct more scientific research on gallbladder cancer to prolong the survival period for patients suffering this lethal malignancy. Because of the important role of Long non-coding RNA (lncRNA) in gene regulation, lncRNA has become a new hotspot in the field of cancer research. Our research team originally conducted the first research about both lncRNA and gallbladder cancer, and published the first relevant paper. Furthermore, in our previous work, a novel LncRNA-MNX1-AS1 has been identified to promote proliferation and invasion of gallbladder cancer cells. Meanwhile, according to our previous finding, we believe that LncRNA-MNX1-AS1 might play its biological role via a ceRNA machenism. In this study, we plan to prove this hypothesis and find out the downstream network of LncRNA-MNX1-AS1. Moreover, its diagnostic and therapeutic role in gallbladder cancer will be determined by various methods and experiments. By conducting this project, hopefully, we could demonstrate both the molecular mechanism of LncRNA-MNX1-AS1 and the its potential role in future diagnosis and therapy.

胆囊癌是胆道系统最常见恶性肿瘤，其诊治效果差、预后不佳，积极开展胆囊癌相关研究对于改善胆囊癌诊治现状意义重大。长链非编码RNA（lncRNA）在基因调控中扮演重要角色，已经成为肿瘤研究的新方向。申请者在国际上首次探索了lncRNA在胆囊癌中的生物学功能并进行了相关报道。同时在前期研究中，我们发现了LncRNA-MNX1-AS1具有调控胆囊癌细胞增殖转移的功能，同时我们的研究结果让我们有理由相信ceRNA在LncRNA-MNX1-AS1发挥其肿瘤生物学功能中发挥了重要作用。在本项目中，我们计划证明这一假说并勾勒出LncRNA-MNX1-AS1 下游调控网络，同时我们还拟利用胆囊癌临床样本以及裸鼠模型等对LncRNA-MNX1-AS1的潜在诊断及治疗价值进行评估。希望本次研究可阐明其在胆囊癌增殖转移中的作用、机制以及其在诊断及治疗中的潜在价值。

胆囊癌是胆道系统最常见恶性肿瘤，其诊治效果差、预后不佳、研究水平相对落后，积极开展胆囊癌相关研究对于改善胆囊癌诊治现状意义重大。由于长链非编码RNA（lncRNA）在基因调控中的重要作用，已经成为肿瘤研究的新方向。申请者在国际上首次探索了lncRNA在胆囊癌中的生物学功能并进行了相关报道。同时在前期研究中，我们筛选了在胆囊癌差异表达的lncRNA，并发现了LncRNA-MNX1-AS1具有调控胆囊癌细胞增殖以及转移的功能，其表达水平与患者预后及进展相关。在本项目中，我们进一步从与ceRNA的角度研究LncRNA-MNX1-AS1 的作用机制，lncRNA-MNX1-AS1通过竞争性结合miR-34a/b/c-5p，促进IMP3的表达，从而发挥生物学功能。对其进行下调可显著抑制胆囊癌细胞在动物模型中增殖转移的能力，提示其具有作为治疗靶点的潜力。通过本项目的研究，我们寻找到了调控胆囊癌发生发展的关键分子lncRNA-MNX1-AS1，有望作为胆囊癌的诊断治疗新靶点进行进一步的研究。