Table_1_LINC00152 Promotes Tumor Progression and Predicts Poor Prognosis by Stabilizing BCL6 From Degradation in the Epithelial Ovarian Cancer.docx

Long non-coding RNA 00152 (LINC00152) is tumorigenic in multiple somatic malignancies. However, its prognostic significance and molecular mechanisms in the epithelial ovarian cancer (EOC) remain elusive. Here our study reveals that dysregulation of LINC00152 is a predictor of poor prognosis in patients with EOC and facilitates ovarian tumor growth and metastasis both in vitro and in vivo; the expression of LINC00152 positively correlates with the protein levels of BCL6 in EOC tissues and ovarian tumor cells; LINC00152 binds to Ser333 and Ser343 of BCL6 protein and stabilizes BCL6 from poly-ubiquitination thus facilitating the oncogenic functions in EOC. Moreover, overexpression of the mutant BCL6S333A/S343A fails to rescue the reduced proliferation and invasion caused by the knockdown of endogenous BCL6 in LINC00152-overexpressing cells. Our study might not only offer clues to the network of lncRNA-protein interactions but also provide potential therapeutic targets for the tumor pharmacology.

长链非编码RNA 00152（Long non-coding RNA 00152，LINC00152）在多种实体恶性肿瘤中具有致癌作用。然而，其在上皮性卵巢癌（epithelial ovarian cancer，EOC）中的预后价值与分子机制仍有待阐明。本研究结果显示，LINC00152的表达失调可作为上皮性卵巢癌患者不良预后的预测因子，并可在体内外促进卵巢肿瘤的生长与转移；LINC00152的表达水平与上皮性卵巢癌组织及卵巢肿瘤细胞中BCL6的蛋白含量呈正相关；LINC00152可结合BCL6蛋白的Ser333与Ser343位点，通过抑制其多聚泛素化修饰稳定BCL6蛋白，进而增强其在上皮性卵巢癌中的致癌功能。此外，在过表达LINC00152的细胞中，敲低内源性BCL6会导致细胞增殖与侵袭能力显著下降，而过表达突变体BCL6S333A/S343A无法挽救这一表型。本研究不仅为长链非编码RNA-蛋白质相互作用网络的解析提供了新的研究线索，也为肿瘤药理学研究提供了潜在的治疗靶点。