长链非编码RNA-MIR503HG在结直肠癌增殖、侵袭和转移中的作用及机制研究

lncRNA-MIR503HG is a long non-coding RNA which serve as a new tumor promoter in colorectal cancer. Our previous study found that the expression of lncRNA-MIR503HG was up-regulated and was associated with poor prognosis in colorectal cancer (CRC). It could promote the proliferation and invasion of CRC cells. However, the specific mechanism is unknown. Based on literature review and our preliminary research, we speculate that lncRNA-MIR503HG may promote CRC prolieration, invasion and metastasis via regulating miR-503/FOSL2. To test this hypothesis, we decide to carry out following research. First, we will analyze the association of lncRNA-MIR503HG and clinicopathological features in colorectcal cancer. Besides that, we will investigate the influence of lncRNA-MIR503HG/miR-503/FOSL2 on CRC proliferation, invasion and metastasis. Then, the possible interactions of lncRNA-MIR503HG/miR-503/FOSL2 axis wil be investigated. This study aims to elucidate the molecular mechanism how lncRNA-MIR503HG promote CRC proliferation, invasion and metastasis and provide scientific basis for lncRNA-MIR503HG acting as a novel target of targeted therapy for CRC.

lncRNA-MIR503HG是本课题组新近在结直肠癌中发现的促癌长链非编码RNA。前期研究发现lncRNA-MIR503HG在结直肠癌组织中高表达且提示预后不良，体内外实验证实lncRNA-MIR503HG能促进结直肠癌细胞增殖和侵袭，但机制不明。结合文献和我们的研究基础，我们提出如下假设：lncRNA-MIR503HG通过调控miR-503/FOSL2促进结直肠癌的增殖、侵袭和转移。本项目拟首先通过临床标本明确lncRNA-MIR503HG在临床中的意义，继而通过体内外实验观察lncRNA-MIR503HG/miR-503/FOSL2调控轴对结直肠癌生物学特性的影响，并探讨lncRNA-MIR503HG/miR-503/FOSL2调控轴可能的相互作用关系。本课题旨在阐明lncRNA-MIR503HG促进结直肠癌增殖、侵袭及转移的分子机制，为结直肠的临床诊疗提供新的思路。

长非编码RNAs(lncRNAs)在肿瘤进展中起着至关重要的作用，这一点已经得到公认。识别失调的lncRNAs及其在癌症中的作用已引起越来越多的关注。然而，这些转录物的功能和导致其在结直肠癌（CRC）中失调的机制仍有待研究。在本研究中，我们旨在探索MIR503HG在CRC中的作用和潜在机制。我们发现，MIR503HG在CRC组织和细胞系中明显上调。它的表达与CRC的肿瘤大小、淋巴结转移、远端转移、TNM晚期和不良生存率有关。在功能上，MIR503HG的沉默抑制了CRC细胞在体外和体内的增殖、侵袭和转移。在机制上，我们发现H19X的沉默通过miR-503-5p的丢失抑制了癌细胞的恶性表型。进一步研究表明，miR-503-5p通过直接调控下游靶点KANK1参与了CRC的进展。总之，本研究的结果表明，MIR503HG/miR-503-5p/KANK1轴在结直肠癌的进展中具有关键作用，为结直肠癌的治疗提供了有效的预后指标和治疗靶标。