Effect of LncRNA SNHG14 on malignant biological behaviors of lung cancer cells by regulating the microRNA-1276/MAT2A axis

李特1曹晓蕾1*张卓然1占超群1雷俊2

doi:10.16098/j.issn.0529-1356.2026.04.006

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (4) : 434-443. DOI: 10.16098/j.issn.0529-1356.2026.04.006

Effect of LncRNA SNHG14 on malignant biological behaviors of lung cancer cells by regulating the microRNA-1276/MAT2A axis

LI Te¹, CAO Xiao-lei^1*, ZHANG Zhuo-ran¹, ZHAN Chao-qun¹, LEI Jun²

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Abstract

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.

Key words

Small nucleolar RNA host gene 14

/ MicroRNA-1276 / Methionine adenosyltransferase 2A / Lung cancer / Western blotting / Human

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LI Te , CAO Xiao-lei , ZHANG Zhuo-ran , ZHAN Chao-qun , LEI Jun.

Effect of LncRNA SNHG14 on malignant biological behaviors of lung cancer cells by regulating the microRNA-1276/MAT2A axis

[J]. Acta Anatomica Sinica. 2026, 57(4): 434-443 https://doi.org/10.16098/j.issn.0529-1356.2026.04.006

References

[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.

[2] Li Y, Yan B, He S. Advances and challenges in the treatment of lung cancer [J]. Biomed Pharmacother, 2023, 169(23): 1-14.

[3] Dai ZT, Wu YL, Xu T, et al. The role of lncRNA SNHG14 in gastric cancer: enhancing tumor cell proliferation and migration, and mechanisms of CDH2 expression [J]. Cell Cycle, 2023, 22(23-24): 2522-2537.

[4] Xu L, Xu Y, Yang M, et al. LncRNA SNHG14 regulates the DDP-resistance of non-small cell lung cancer cell through miR-133a/HOXB13 pathway [J]. BMC Pulm Med, 2020, 20(1): 266-276.

[5] Zhang L, Zhang Z, Zheng X, et al. A novel microRNA panel exhibited significant potential in evaluating the progression of laryngeal squamous cell carcinoma [J]. Noncoding RNA Res, 2023, 8(4): 550-561.

[6] Sun CC, Zhu W, Li SJ, et al. FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway [J]. Genome Med, 2020, 12(1): 77-104.

[7] Chu PY, Wu HJ, Wang SM, et al. MAT2A localization and its independently prognostic relevance in breast cancer patients [J]. Int J Mol Sci, 2021, 22(10): 5382-5396.

[8] Chen YW, Du QR, He YJ, et al. Circ_0044516 regulates miR-136/MAT2A pathway to facilitate lung cancer development [J]. J Immunol Res, 2021, 15(1): 1-12.

[9] Zhao X, Wang L, Lin H, et al. Inhibition of MAT2A-related methionine metabolism enhances the efficacy of cisplatin on cisplatin-resistant cells in lung cancer [J]. Cell J, 2022, 24(4): 204-211.

[10] Chinese Medical Association, Oncology Branch. Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2024 edition) [J]. Chinese Journal of Oncology, 2024, 46(9): 805-843. (in Chinese)

中华医学会肿瘤学分会. 中华医学会肺癌临床诊疗指南（2024版）[J]. 中华肿瘤杂志, 2024, 46(9): 805-843.

[11] Li Y, Wu X, Yang P, et al. Machine learning for lung cancer diagnosis, treatment, and prognosis [J]. Genom Proteom Bioinform, 2022, 20(5): 850-866.

[12] Zheng Y, Hu J, Li Y, et al. Clinicopathological and prognostic significance of circRNAs in lung cancer: a systematic review and meta-analysis [J]. Medicine (Baltimore), 2021, 100(14): 1-15.

[13] Wen T, Song L, Hua S. Perspectives and controversies regarding the use of natural products for the treatment of lung cancer [J]. Cancer Med, 2021, 10(7): 2396-2422.

[14] Dai J, Qu T, Yin D, et al. LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer [J]. Cell Death Dis, 2023, 14(5): 312-326.

[15] Wang X, Yang P, Zhang D, et al. LncRNA SNHG14 promotes cell proliferation and invasion in colorectal cancer through modulating miR-519b-3p/DDX5 axis [J]. J Cancer, 2021, 12(16): 4958-4970.

[16] Chen X, Song P, Yao Y, et al. Long non-coding RNA SNHG14 regulates SPIN1 expression to accelerate tumor progression in non-small cell lung cancer by sponging miR-382-5p [J]. Cancer Manag Res, 2020, 12(1): 9113-9123.

[17] Hill M, Tran N. MiRNA interplay: mechanisms and consequences in cancer [J]. Dis Model Mech, 2021, 14(4): 1-11.

[18] Li H, Zhang LN, Song RJ, et al. MicroRNA-221 targets tissue inhibitor of metalloproteinases 2 to mediate the Akt/mTOR signaling pathway and affect xenograft tumor models of non-small cell lung cancer in mice [J]. Acta Anatomica Sinica, 2022, 53(6): 754-761. (in Chinese)

李辉, 张丽娜, 宋瑞佳, 等. 微小RNA-221靶向组织金属蛋白酶抑制因子2介导Akt/mTOR信号通路对非小细胞肺癌移植瘤小鼠模型的影响 [J]. 解剖学报, 2022, 53(6): 754-761.

[19] You J, Han Y, Qiao H, et al. Hsa_circ_0063804 enhances ovarian cancer cells proliferation and resistance to cisplatin by targeting miR-1276/CLU axis [J]. Aging (Albany NY), 2022, 14(11): 4699-4713.

[20] Zhang Z, Zhao H, Zhou G, et al. Circ_0002623 promotes bladder cancer progression by regulating the miR-1276/SMAD2 axis [J]. Cancer Sci, 2022, 113(4): 1250-1263.

[21] Xia S, Liang Y, Shen Y, et al. MAT2A inhibits the ferroptosis in osteosarcoma progression regulated by miR-26b-5p [J]. J Bone Oncol, 2023, 41(1): 1-9.

[22] Luo H, Song Y, Zhang JA, et al. MAT2A facilitates PDCD6 methylation and promotes cell growth under glucose deprivation in cervical cancer [J]. Cell Death Discov, 2022, 8(1): 176-186.

[23] Cacciatore A, Shinde D, Musumeci C, et al. Epigenome-wide impact of MAT2A sustains the androgen-indifferent state and confers synthetic vulnerability in ERG fusion-positive prostate cancer [J]. Nat Commun, 2024, 15(1): 6672-6697.