miR-148a和miR-409在胃癌中的低表达对胃癌转移相关基因的影响及其干预治疗研究

In recent years, studies confirm that microRNA(miRNA) plays an important role in tumor initiation、progression and metastasis, and also suggests that miRNA has a great therapeutic potential for cancer management. Our previous work found that miR-148a and miR-409 were both significantly downregulated in gastric cancer, and overexpression of miR-148a and miR-409 suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo through the regulation of the target gene ROCK1 and RDX respectively. Therefore, we propose the hypothesis: miR-148a and miR-409 may target other metastasis-related genes in gastric cancer progression, and miR-148a and miR-409 have therapeutic value for treating gastric cancer metastasis. To verify our idea,, we will further explore the mechanisms of miR-148a and miR-409 in gastric cancer invasion and metastasis by molecular biology assays、cell assays and human tissue assays. To clarify the value of their preclinical applications, we transport miR-148a or miR-409 into mouse through the tail vein or abdominal cavity by the biological carrier, and observe the effects of miR-148a or miR-409 on gastric cancer cell metastasis and peritoneal dissemination in mouse model. This study from miRNA this new viewpoint to continue to reveal the mechanism of miR-148a and miR-409 in gastric cancer metastasis,and focus on the clinical translational research of miR-148a and miR-409 in mouse models, our study will provide new ideas and application approaches to treat advanced gastric cancer with invasion and metastasis.

近些年研究证实miRNA在肿瘤的发生发展及转移中起着重要作用，还提示有较大治疗潜能。我们前期工作发现miR-148a和miR-409在胃癌中均低表达，分别通过调控靶基因ROCK1和RDX抑制胃癌细胞迁移、侵袭和小鼠肺转移能力。据此，我们提出假设：miR-148a和miR-409在胃癌进展过程中可能对其他转移基因起着靶向调控作用，并可能具有潜在治疗胃癌侵袭转移价值。为此，我们将从分子、细胞和组织水平继续挖掘miR-148a和miR-409在胃癌侵袭转移中的作用机制，并利用生物载体通过小鼠尾静脉或腹腔注射miR-148a或miR-409，观察对小鼠体内胃癌细胞肺转移和腹腔种植的影响，从而明确其临床前期应用价值。本研究将继续深入剖析miR-148a和miR-409在胃癌侵袭转移中的作用机制，并致力于miR-148a和miR-409的临床转化研究，为进展期胃癌侵袭转移的治疗提供新的思路和应用前景。

miRNA在肿瘤中发挥着重要作用，与肿瘤形成、进展和预后密切相关。在本研究中，通过对87对胃癌组织及其癌旁组织miR-378表达水平检测和分析，发现：miR-378在胃癌中低表达，且其表达水平越低，肿瘤浸润深度越深，淋巴结越容易转移，肿瘤分期越高，患者预后越差。本研究提示miR-378可作为判断胃癌患者肿瘤侵袭进展和预后的一个有用指标。..腱鞘巨细胞瘤属于软组织肿瘤中的一种类型，也称为“巨细胞滑膜瘤”和“局限性结节性腱鞘炎”。肿块质韧，直径一般1-3厘米，常附着在手指、手、腕关节的肌腱上，手腕的屈肌肌腱更多见，好发于20-50岁患者的手指和腕关节，通常是无痛的，并导致骨侵蚀破坏，此种肿瘤容易复发。本研究通过转录组测序发现一个新的融合基因（CCL3L1-TBC1D3B），该融合基因的发现对了解腱鞘巨细胞瘤发病机制具有重要作用。