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

Yue Li; Jian Zhao; Weijie Zhang; Anqi Wang; Min Jiao; Xin Cai; Jianjie Zhu; Zeyi Liu; Jian-An Huang

doi:10.1080/15384101.2022.2101336

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

Cell Cycle. 2022 Dec;21(23):2455-2470. doi: 10.1080/15384101.2022.2101336. Epub 2022 Jul 19.

Authors

Yue Li^{1

2}, Jian Zhao^{1

2}, Weijie Zhang^{1

2}, Anqi Wang^{1

2}, Min Jiao^{1

2}, Xin Cai^{1

2}, Jianjie Zhu^{1

2

3}, Zeyi Liu^{1

2

3}, Jian-An Huang^{1

2

3}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Institute of Respiratory Diseases, Soochow University, Suzhou, China.
³ Suzhou Key Laboratory for Respiratory Diseases, Suzhou, China.

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.

Keywords: CeRNA; GALNT3; LINC02535; LUAD; MiR-30a-5p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / genetics
Animals
Carcinoma, Hepatocellular* / pathology
Carcinoma, Non-Small-Cell Lung* / genetics
Cell Line, Tumor
Cell Proliferation / genetics
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms* / pathology
Lung / metabolism
Lung Neoplasms* / pathology
Mice
MicroRNAs* / genetics
MicroRNAs* / metabolism
NF-kappa B / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Signal Transduction
Transferases / genetics
Transferases / metabolism

Substances

RNA, Long Noncoding
NF-kappa B
MicroRNAs
Transferases

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82073213), The Suzhou Gusu Medical Youth Talent (GSWS2020016), The Science and Technology Development Projects of Suzhou (No. SZYJTD201801).