LncRNA SNHG6调控STMN1/p27Kip1促进卵巢癌恶性进展的作用和机制研究

Ovarian high grade serous carcinoma (HGSOC) is the predominant pathological subtype of ovarian epithelial carcinoma and the most fatal malignancy in female but the underlying pathogenesis remains unclear. In our preliminary research, we found that LncRNA SNHG6 expression is upregulated in ovarian HGSOC by studying the transcriptome of HGSOC and fallopian tubal epithelium via RNA sequencing. The high expression of SNHG6 is correlated with adverse prognosis of this disease. In vitro, SNHG6 inhibition suppresses the malignant phenotype of cancer cell, boosts Cisplatin sensitivity and leads to change of early signals of HGSOC, including STMN1 and p27Kip1, suggesting the key role of SNHG6 in HGSOC progression and Cisplatin chemo-resistance. SNHG6’s role in pathogenesis and chemo-resistance in ovarian cancer has not been reported before. Based upon our preliminary data, we plan to undertake experiments, including in vivo and in vitro functional study, RNA immunoprecipitation and dual luciferase reporter test, et al. to investigate SNHG6’s competitive binding with miR-26a-5p, the potential regulator of STMN1, and further regulation STMN1/p27Kip1 and downstream pathway signals. We believe that this study of SNHG6’s role and mechanism in promoting HGSOC progression and chemo-resistance would provide theoretical basis for translational research regarding early detection and individualized precision therapy of this deadly disease.

卵巢高级别浆液性癌（HGSOC）是卵巢癌最主要的亚型，死亡率居妇科肿瘤之首，但发病机制尚不明确。近年发现该疾病大部分可起源于输卵管上皮。本课题预实验通过RNA-Seq研究HGSOC与输卵管上皮转录组差异，发现LncRNA SNHG6在HGSOC中高表达并与不良预后有关，敲低SNHG6可抑制癌细胞的恶性表型，调节该疾病早期信号STMN1/p27Kip1，并增敏顺铂，提示SNHG6是促进HGSOC恶性进展和顺铂耐药的关键基因。基于此发现及SNHG6在卵巢癌发病和耐药机制方面尚无报道，本课题拟开展体内、外功能验证、RNA免疫共沉淀、双荧光素酶基因检测等实验，研究SNHG6与STMN1调控因子miR-26a-5p的竞争结合，进而调控STMN1/p27Kip1及其下游通路的分子机制。本课题对SNHG6促进HGSOC恶性进展和耐药机制的研究可能为该疾病的早期诊断及精准治疗等转化研究提供理论和实验依据。

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