Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
Molecular Medicine Research Center, Chang Gung University, Taoyuan 244, Taiwan.
Cells. 2022 Aug 22;11(16):2610. doi: 10.3390/cells11162610.
Tumor metastasis is a complex process modulated by both intrinsic and extrinsic factors that ultimately result in poorer patient outcomes, including diminished survival. Pseudogene-derived long non-coding RNAs (lncRNA) play important roles in cancer progression. In the current study, we found that the pseudogene-derived lncRNA LPAL2 is downregulated in hepatocellular carcinoma (HCC) tissues, and further showed that elevated LPAL2 expression is positively correlated with survival outcome. The knockdown of LPAL2 in hepatoma cells induced tumor formation, migration, invasion, sphere formation, and drug resistance. Metalloproteinase 9 () was identified as an LPAL2-regulated target gene, consistent with clinical findings that LPAL2 expression is significantly associated with MMP9 expression. Furthermore, patients with a higher expression of LPAL2 and lower expression of MMP9 (LPAL2-high/MMP9-low) had a higher survival rate than those with other combinations. Collectively, our findings establish LPAL2 as a novel tumor suppressor in HCC, and suggest targeting LPAL2 and MMP9 as a therapeutic approach for the treatment of HCC.
肿瘤转移是一个复杂的过程，受内在和外在因素的调节，最终导致患者预后较差，包括生存时间缩短。假基因衍生的长非编码 RNA（lncRNA）在癌症进展中发挥重要作用。在本研究中，我们发现假基因衍生的 lncRNA LPAL2 在肝癌（HCC）组织中表达下调，并进一步表明 LPAL2 表达水平的升高与生存结局呈正相关。在肝癌细胞中敲低 LPAL2 会诱导肿瘤形成、迁移、侵袭、球体形成和耐药性。金属蛋白酶 9（）被鉴定为 LPAL2 调控的靶基因，与 LPAL2 表达与 MMP9 表达显著相关的临床发现一致。此外，LPAL2 高表达和 MMP9 低表达（LPAL2-high/MMP9-low）的患者的生存率高于其他组合。总之，我们的研究结果确立了 LPAL2 作为 HCC 中的一种新型肿瘤抑制因子，并提示靶向 LPAL2 和 MMP9 可能是治疗 HCC 的一种治疗方法。
