Linc00426 accelerates lung adenocarcinoma progression by regulating miR-455-5p as a molecular sponge

Abstract

Increasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.

Identification of Novel Tumor Microenvironment-Related Long Noncoding RNAs to Determine the Prognosis and Response to Immunotherapy of Hepatocellular Carcinoma Patients

“…Some of the lncRNAs in this risk model have already been identified as involved in the malignant phenotypes of HCC or other cancers. For instance, LINC00426 was significantly upregulated in lung adenocarcinoma and played a notable role in accelerating tumor proliferation, invasion, metastasis, and EMT in vitro and in vivo (Li et al, 2020) microenvironment, which is positively associated with Th cell differentiation, cytokine signaling pathways, and multiple immune markers, including cytotoxic markers, co-inhibitory and co-stimulatory molecules (i.e., PD1, CTLA4, HAVCR2, TIGIT, FOXP3, and ICOS), and chemokine receptors and ligands (i.e., CXCR3/6, CXCL9/13, CCL4/5/7/19, and CCR7) (Wang et al, 2021b). LINC002273 was reported to be correlated with tumor proliferation, migration, and invasion by epigenetically increasing the AGR2 transcription in breast cancer (Xiu et al, 2019).…”

Immune Milieu and Genomic Alterations Set the Triple-Negative Breast Cancer Immunomodulatory Subtype Tumor Behavior

“…In this regard, MSL cells promote inflammation when the immune system is not fully activated or limit inflammation if the immune system is overwhelmed as it fights cancer [ 49 ]. Of those seven lincRNAs, LINC01550 and LINC00426 were identified as oncogenesis regulators in non-BC tumors [ 50 , 51 ] and only three (LINC00173, LINC00861, LINC00312) were identified in BC [ 52 , 53 , 54 ]. However, we found evidence of association in four regarding tumor immune regulation: LINC00426, LINC00173, LINC00861, and LINC00312.…”

Identification of Novel Tumor Microenvironment-Related Long Non-coding RNAs to Predict the Prognosis for Hepatocellular Carcinoma

“…Some lncRANs in this risk model have been illuminated to be involved in the progression of HCC or other cancers, including LINC00426 and LINC02273. Previous study have demonstrated that the expression of LINC00426 was signi cantly down-regulated in the tumor tissue of including 72 NSCLC patients compared to normal lung tissue and the expression level was also remarkably correlated with the clinical stage [26].In contrast, another study showed an opposite result, the LINC00426 was signi cantly upregulated in lung adenocarcinoma(LUAD) tissues and cell lines and play a notable role in accelerating tumor proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) in vitro and in vivo, which via regulating the miR-455-5p/ UBE2V1 [27]. Besides, it has been reported that LINC00426 is also a key regulator in doxorubicin resistance of osteosarcoma [28].…”