Long noncoding RNA LINC00518 contributes to proliferation and metastasis in lung adenocarcinoma via the miR-335-3p/CTHRC1 Axis

Ruoyi Shen,Ruochen Zhang,Weijie Zhang,Jianjie Zhu,Jian-An Huang,Yuanyuan Zeng,Dan Shen,Zeyi Liu,Xin Cai,Anqi Wang,Yue Li,Yang Zhang

doi:10.1038/s41420-022-00905-w

Abstract

Long intergenic nonprotein coding RNA 518 (LINC00518) is recognized to impart cancer proliferation and metastasis in lung adenocarcinoma (LUAD). However, the study about the relationship between LINC00518 and LUAD is shallow so far. In our work, LINC00518 was predicted to be a negative regulator in LUAD based on the TCGA database. It was further verified that the cell proliferation, colony formation, migration, and invasion of LUAD could be obviously inhibited by the knockdown of LINC00518. Moreover, miR-335-3p/CTHRC1 axis was intensively possible to be a critical regulator in the effect of LINC00518 on LUAD via visual ceRNA network. Importantly the progress of LUAD was relevant to the active CTHRC1 which was realized by the target of LINC00518 to miR-335-3p. Furthermore, the knockdown of LINC00518 exhibited a synergistic effect with VS6063, an inhibitor of FAK protein, in the suppression of LUAD indicating that miR-335-3p/CTHRC1 axis was potentially exploitable as a targeted intervention to integrin β3/FAK signal pathway in LUAD. All the collective results demonstrated that LINC00518 could be a promising biomarker of the prognosis of LUAD and possibly a therapeutic target via miR-335-3p/CTHRC1 axis.

Highlights

In nowadays society, lung cancer remains at the top of the list of tumor-related deaths around the world, and its incidence has increased steadily by 10% annually [1, 2]
This study aims to identify that LINC00518 sponges miR-335-3p invasion to activate Collagen triple helix repeat containing 1 (CTHRC1) transcription and integrinβ3/focal adhesion kinase (FAK) signaling, First, in A549 and H1299 cells, we detected the expression of which are required for lung adenocarcinoma (LUAD) proliferation and metastasis
As crucial regulators in multiple cellular processes associated with tumorigenesis and metastasis, in the past decades, Long noncoding RNAs (lncRNAs) have drawn great much attention and interest [22, 23]

Summary

Introduction

Lung cancer remains at the top of the list of tumor-related deaths around the world, and its incidence has increased steadily by 10% annually [1, 2]. NSCLC accounts for around 85% of lung cancers, and includes adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, and large cell carcinoma; SCLC accounts for 15% of lung cancers [3]. The mechanism of proliferation, metastasis, and drug resistance of LUAD should be explored extremely urgently. Long intergenic nonprotein coding RNA 518 (LINC00518), has been known to promote and up-regulate cancer cell proliferation and metastasis in cervical cancer, breast cancer, and malignant melanoma [6, 7]. It makes a contribution to chemotherapeutic drug resistance in prostate cancer and breast cancer [8, 9]. It could induce radioresistance by regulating glycolysis in melanoma [10]. Some researchers have shown that LINC00518 acts as an oncogene to facilitate tumor progression in NSCLC by regulating an RNA-based network [11]. The accurate role and molecular mechanism of LINC00518 in LUAD are still undetermined

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