LINC02535/miR-30a-5p/GALNT3 axis contributes to lung adenocarcinoma progression via the NF- κ B signaling pathway

Abstract

ABSTRACT 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. In vitro 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 in vivo. 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. Abbreviations: 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.