[摘 要] 目的：探究长链非编码RNA（lncRNA）小核仁RNA宿主基因14（SNHG14）靶向miR-579-3p/富含半胱氨酸的酸性分 泌蛋白（SPARC）对肝细胞癌（HCC）细胞恶性生物学行为的影响。方法：常规培养人正常肝细胞（LO2）和HCC细胞Huh7、 Hep3B、HepG2，将Huh7细胞随机分为对照组、sh-NC组、sh-SNHG14组、sh-SNHG14 + anti-NC组和sh-SNHG14 + anti-miR-579-3p 组，qPCR法检测细胞中SNHG14、miR-579-3p和SPARC mRNA的表达水平，双萤光素酶报告基因实验验证SNHG14与 miR-579-3p及miR-579-3p与SPARC调控关系，MTT法、划痕愈合实验、Transwell实验、流式细胞术，以及WB法分别检测各组 Huh7细胞的增殖、迁移、侵袭能力、凋亡，以及Huh7细胞中PCNA、E-cadherin、vimentin、SPARC蛋白的表达。结果：在HCC细胞 中SNHG14、SPARC mRNA呈高表达、miR-579-3p呈低表达（均P < 0.05）；SNHG14与miR-579-3p和miR-579-3p与SPARC mRNA 间存在直接结合调控关系（均P < 0.05）。敲减SNHG14可明显抑制Huh7细胞的增殖、迁移、侵袭、PCNA、vimentin、SPARC mRNA及蛋白的表达（均P < 0.05），促进细胞凋亡、miR-579-3p和E-cadherin表达（均P < 0.05）；抑制miR-579-3p则可部分逆转敲 减SNHG14对Huh7细胞的作用（均P < 0.05）。结论：敲减SNHG14可通过靶向miR-579-3p/SPARC轴抑制Huh7细胞的恶性生 物学行为，促进其凋亡；SNHG14和miR-579-3p/SPARC轴可能是HCC治疗的潜在靶点。

[Abstract] Objective: To investigate the effects of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) on the malignant biological behavior of hepatocellular carcinoma (HCC) cells by targeting miR-579-3p/secreted protein acidic and rich in cysteine (SPARC) axis. Methods: Normal human hepatocytes (LO2) and HCC cells (Huh7, Hep3B, HepG2) were routinely cultured. Huh7 cells were randomly divided into control, sh-NC, sh-SNHG14, sh-SNHG14 + anti-NC, and sh-SNHG14 + anti-miR-579-3p groups. The mRNA expression levels of SNHG14, miR-579-3p, and SPARC in the above cells were detected by qPCR. Dual-luciferase reporter gene assay was applied to verify the regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579 3p and SPARC. The proliferation, migration, invasion, and apoptosis of Huh7 cells in each group were assessed using MTT, wound healing, Transwell, and flow cytometry assays, respectively. WB was used to detect the protein levels of PCNA, E-cadherin, vimentin, and SPARC. Results: In HCC cells, SNHG14 and SPARC mRNA were upregulated, whereas miR-579-3p was downregulated (all P < 0.05). There was a direct binding regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579-3p and SPARC mRNA (all P < 0.05). Knockdown of SNHG14 significantly inhibited the proliferation, migration, invasion, and the expression of PCNA and vimentin, as well as the mRNA and protein expression of SPARC in Huh7 cells (all P < 0.05), while promoting apoptosis, expression of miR-579-3p, and E-cadherin expression (all P < 0.05). Inhibition of miR-579-3p partially reversed the effects of SNHG14 knockdown on Huh7 cells (all P < 0.05). Conclusion: Knockdown of SNHG14 can inhibit the malignant biological behaviors of Huh7 cells and promote their apoptosis by targeting the miR-579-3p/SPARC axis. The SNHG14/miR-579-3p/SPARC axis may represent a potential therapeutic target for HCC.

[基金项目] 武汉市卫生健康委员会资助项目（No. WX21D19）