目的 探讨长链非编码RNA核内小RNA宿主基因14（LncRNA SNHG14）调节微RNA-1276（miR-1276）/甲硫氨酸腺苷转移酶2A（MAT2A）轴对肺癌细胞恶性生物学行为的影响。方法 Real-time PCR检测肺癌患者癌组织、癌旁组织及人肺癌细胞A549、NCI-H1299和正常肺上皮细胞BEAS-2B中SNHG14、miR-1276和MAT2A mRNA水平。A549、NCI-H1299细胞分为对照（Ctrl）组、小干扰阴性对照（si-NC）组、si-SNHG14组、si-SNHG14+anti-miR-NC组、si-SNHG14+anti-miR-1276组。采用集落形成实验、5-乙炔基-2-脱氧尿苷（EdU）法检测细胞增殖，流式细胞术检测细胞凋亡，Transwell实验检测细胞迁移和侵袭，Western blotting检测细胞周期蛋白D1（Cyclin D1）、增殖标志物Ki-67（Ki-67）、Caspase-3、Bax、MAT2A蛋白表达情况，双荧光素酶实验和RNA沉淀（pull-down）实验检测SNHG14与miR-1276、miR-1276与MAT2A靶向关系。结果 与癌旁组织相比，肺癌组织中SNHG14、MAT2A mRNA表达水平升高，miR-1276表达水平降低（P＜0.05）；与BEAS-2B细胞相比，A549、NCI-H1299细胞SNHG14、MAT2A mRNA水平升高，miR-1276水平降低（P＜0.05）；与si-NC组相比，si-SNHG14组细胞中SNHG14、MAT2A mRNA及其蛋白表达量减少，集落形成率、EdU阳性率、迁移和侵袭细胞数、Cyclin D1、Ki-67蛋白表达量降低，miR-1276表达水平、细胞凋亡率及Caspase-3、Bax蛋白表达量升高（P＜0.05）；与si-SNHG14+anti-miR-NC组相比，si-SNHG14+anti-miR-1276组细胞集落形成率、EdU阳性率、迁移细胞数、侵袭细胞数升高，MAT2A mRNA表达水平升高，MAT2A、Cyclin D1、Ki-67蛋白表达量升高，miR-1276表达水平、细胞凋亡率及Caspase-3、Bax蛋白表达量降低（P＜0.05）。SNHG14可作为分子海绵吸附miR-1276，而miR-1276能够直接靶向并抑制MAT2A的表达。结论 下调LncRNA SNHG14可通过调节miR-1276/MAT2A轴抑制肺癌细胞恶性生物学行为。

Objective To investigate effect of long non-coding RNA small nucleolar RNA host gene 14 (LncRNA SNHG14) on malignant biological behaviors of lung cancer cells by regulating the microRNA-1276 (miR-1276)/methionine adenosyltransferase 2A (MAT2A) axis. Methods Real-time PCR was used to measure SNHG14, miR-1276, and MAT2A mRNA levels in lung cancer tissue, adjacent non-tumor tissues, and in human lung cancer cell lines A549 and NCI-H1299, as well as normal alveolar epithelial cell line BEAS-2B. A549 and NCI-H1299 cells were allocated into the following groups, control(Ctrl), small interfering negative Control (si-NC), si-SNHG14, si-SNHG14 + anti-microRNA negative control (anti-miR-NC), and si-SNHG14 + anti-miR-1276. Colony formation assay and 5-ethynyl-2’-deoxyuridine(EdU)assay were used to assess cell proliferation; Flow cytometry was used to detect apoptosis; Transwell assay was used to assess migration and invasion. Western blotting was used to determine protein expression of Cyclin D1, marker of proliferation Ki-67 (Ki-67), Caspase-3, Bax, and MAT2A. Dual-luciferase reporter assay and RNA pull-down assay were employed to confirm the targeting relationships between SNHG14 and miR-1276, and between miR-1276 and MAT2A. Results Compared with adjacent non-tumor tissue, lung cancer tissue had higher expression of SNHG14 and MAT2A mRNA, and lower expression of miR-1276 (P<0.05). Compared with BEAS-2B cells, A549 and NCI-H1299 cells exhibited higher SNHG14 and MAT2A mRNA levels and lower miR-1276 levels (P<0.05). In si-SNHG14-treated cells, SNHG14 and MAT2A mRNA and protein levels were reduced relative to the si-NC group, along with decreased colony formation rate, EdU positivity, migration and invasion, and lower expression of Cyclin D1 and Ki-67; miR-1276 expression and apoptosis rate, as well as Caspase-3 and Bax protein levels increased (P<0.05). Compared with si-SNHG14 + anti-miR-NC, the si-SNHG14 + anti-miR-1276 group showed increased colony formation, EdU positivity, and numbers of migrating and invading cells, higher MAT2A mRNA expression, and elevated MAT2A, Cyclin D1, and Ki-67 protein levels, while miR-1276 expression, apoptosis rate, and Caspase-3 and Bax protein levels decreased (P<0.05). SNHG14 acted as a molecular sponge to sequester miR-1276, while miR-1276 directly targets and inhibits MAT2A expression. Conclusion Downregulation of LncRNA SNHG14 suppresses malignant biological behaviors of lung cancer cells by modulating the miR-1276/MAT2A axis.