Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Respiratory Diseases, Soochow University, Suzhou, China.
Cell Cycle. 2022 Dec;21(23):2455-2470. doi: 10.1080/15384101.2022.2101336. Epub 2022 Jul 19.
Long non-coding RNAs (LncRNA) play important roles in multiple types of cancers. We addressed the role of LINC02535 by regulating the miR-30a-5p /GalNAc Transferase 3 (GALNT3) axis to promote the proliferation, migration, and invasion in lung adenocarcinoma (LUAD) cells. The Cancer Genome Atlas (TCGA) database screened differentially expressed lncRNAs. Quantitative real-time PCR analysis (qRT-PCR) confirmed that LINC02535 is highly expressed in LUAD tissues and cells. experiments showed that LINC02535 promotes the proliferation, migration, and invasion of LUAD cells. A xenograft mouse model was used to show that LINC02535 promotes tumor growth . RNA immunoprecipitation (RIP) and Dual-luciferase reporter assay results confirmed that LINC02535 targets miR-30a-5p. The Vicia villosa lectin (VVA) pull-down assay indicated that MUC1 is the glycosylation target of GALNT3, and western blot verified that NF-κB is the downstream signaling pathway of MUC1. We found that LINC02535 was increased in LUAD tissues and cells, and LINC02535 was correlated with the poor prognosis of LUAD patients. miR-30a-5p acts as a tumor suppressor in LUAD by targeting GALNT3. We also demonstrated that LINC02535 might function as the sponge of miR-30a-5p to up-regulate GALNT3, and consequently promote the proliferation and metastasis of LUAD. LINC02535 acts as a competing endogenous RNA (ceRNA) to interact with miR-30a-5p, thereby upregulating the expression of GALNT3, enhancing the function of MUC1, and activating the NF-κB signaling pathway, promoting the malignant progression of LUAD cells. LncRNA:long non-coding RNA; LUAD: lung adenocarcinoma; TCGA: The Cancer Genome Atlas; GALNT3: GalNAc Transferase 3; qRT-PCR: quantitative real-time PCR analysis; RIP: RNA immunoprecipitation; SPF: specific pathogen-free; VVA: Vicia villosa lectin; ceRNA: competing endogenous RNA; MiRNAs: microRNAs; FBS: fetal bovine serum; PBS: Phosphate buffered saline; CCK-8: Cell Counting Kit-8; NSCLC: non-small cell lung cancer; OC: ovarian cancer; HCC: hepatocellular carcinoma.
长链非编码 RNA（LncRNA）在多种类型的癌症中发挥重要作用。我们通过调控 miR-30a-5p/GalNAc 转移酶 3（GALNT3）轴来研究 LINC02535 的作用，以促进肺腺癌（LUAD）细胞的增殖、迁移和侵袭。癌症基因组图谱（TCGA）数据库筛选差异表达的 lncRNA。实时荧光定量 PCR（qRT-PCR）分析证实 LINC02535 在 LUAD 组织和细胞中高表达。实验表明，LINC02535 促进 LUAD 细胞的增殖、迁移和侵袭。利用异种移植小鼠模型表明，LINC02535 促进肿瘤生长。RNA 免疫沉淀（RIP）和双荧光素酶报告基因实验结果证实 LINC02535 靶向 miR-30a-5p。麦胚凝集素（VVA）拉曼验证表明 MUC1 是 GALNT3 的糖基化靶标，Western blot 验证 NF-κB 是 MUC1 的下游信号通路。我们发现 LINC02535 在 LUAD 组织和细胞中增加，并且 LINC02535 与 LUAD 患者的不良预后相关。miR-30a-5p 通过靶向 GALNT3 作为 LUAD 的肿瘤抑制因子发挥作用。我们还表明，LINC02535 可能作为 miR-30a-5p 的海绵发挥作用，上调 GALNT3，从而促进 LUAD 的增殖和转移。LINC02535 作为竞争性内源性 RNA（ceRNA）与 miR-30a-5p 相互作用，从而上调 GALNT3 的表达，增强 MUC1 的功能，激活 NF-κB 信号通路，促进 LUAD 细胞的恶性进展。LncRNA：长链非编码 RNA；LUAD：肺腺癌；TCGA：癌症基因组图谱；GALNT3：GalNAc 转移酶 3；qRT-PCR：实时荧光定量 PCR 分析；RIP：RNA 免疫沉淀；SPF：无特定病原体；VVA：麦胚凝集素；ceRNA：竞争性内源性 RNA；miRNAs：微小 RNA；FBS：胎牛血清；PBS：磷酸盐缓冲液；CCK-8：细胞计数试剂盒-8；NSCLC：非小细胞肺癌；OC：卵巢癌；HCC：肝细胞癌。
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