Hepatocellular carcinoma (HCC) is a lethal malignancy with few effective options for therapeutic treatment in its advanced stages. While exosomal LINC00161 has been identified as a potential biomarker for HCC, its regulatory function and clinical values remain largely unknown. LINC00161 expressions in serum-derived exosomes from HCC patients and HCC cells were determined by qRT-PCR. The ability of proliferation, migration, and angiogenesis in HUVECs was assessed by MTT, Transwell, and tube formation. Luciferase reporter assay and AGO2-RIP assay were conducted to explore the interactions among LINC00161, miR-590-3p, and ROCK2. The level of ROCK signal-related proteins was examined by Western blotting and immunohistochemistry (IHC) assay. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of HCC cells. High levels of LINC00161 were detected in both serum-derived exosomes from HCC patients and the supernatants of HCC cell lines and were significantly associated with poor survival. Functional study demonstrated that exosomal LINC00161 derived from HCC-cells were significantly associated with enhanced proliferation, migration, and angiogenesis in HUVECs in vitro, all of which were effectively inhibited when LINC00161 was sliced with shRNA in HCC-cells. In vivo experiment showed that LINC00161 loss inhibited tumorigenesis and metastasis of HCC. Mechanistic study revealed that exosome-carried LINC00161 directly targeted miR-590-3p and induced its downstream target ROCK2, finally activating growth/metastasis-related signals in HCC. Exosome-carried LINC00161 promotes HCC tumorigenesis through inhibiting miR-590-3p to activate the ROCK2 signaling pathway, suggesting that LINC00161 may be used as potential targets to improve HCC treatment efficiency.

肝细胞癌 (HCC) 是一种致命的恶性肿瘤，在其晚期阶段几乎没有有效的治疗选择。虽然外泌体 LINC00161 已被确定为 HCC 的潜在生物标志物，但其调节功能和临床价值仍然很大程度上未知。通过 qRT-PCR 测定来自 HCC 患者和 HCC 细胞的血清来源外泌体中的 LINC00161 表达。通过 MTT、Transwell 和管形成评估 HUVEC 的增殖、迁移和血管生成能力。进行荧光素酶报告基因测定和 AGO2-RIP 测定以探索 LINC00161、miR-590-3p 和 ROCK2 之间的相互作用。通过蛋白质印迹和免疫组织化学 (IHC) 测定法检查 ROCK 信号相关蛋白的水平。在裸鼠中观察到皮下肿瘤生长，其中尾静脉注射 HCC 细胞后观察到体内转移。在 HCC 患者的血清来源外泌体和 HCC 细胞系上清液中检测到高水平的 LINC00161，并且与较差的存活率显着相关。功能研究表明，源自 HCC 细胞的外泌体 LINC00161 在体外与 HUVEC 中增强的增殖、迁移和血管生成显着相关，当 LINC00161 在 HCC 细胞中用 shRNA 切片时，所有这些都被有效抑制。体内实验表明，LINC00161 缺失抑制了 HCC 的肿瘤发生和转移。机制研究表明，携带外泌体的 LINC00161 直接靶向 miR-590-3p 并诱导其下游靶标 ROCK2，最终激活 HCC 中生长/转移相关信号。