LINC02535/miR-30a-5p/GALNT3 轴通过 NF-κB 信号通路促进肺腺癌的进展。
LINC02535/miR-30a-5p/GALNT3 axis contributes to lung adenocarcinoma progression via the NF- κ B signaling pathway.
机构信息
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Respiratory Diseases, Soochow University, Suzhou, China.
出版信息
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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