A long non-coding RNA LINC00461-dependent mechanism underlying breast cancer invasion and migration via the miR-144-3p/KPNA2 axis

Abstract

Background: The purpose of this study was to explore the regulatory mechanism of the long non-coding RNA (lncRNA) LINC00461 underlying the breast cancer invasion and migration via the miR-144-3p/KPNA2 axis. Methods: Bioinformatics methods were applied to screen differentially expressed mRNAs, miRNAs and lncRNAs for construction of a competing endogenous RNA (ceRNA) network. LINC00461, KPNA2 and miR-144-3p were identified, and KPNA2 was predicted to be a target of miR-144-3p and significantly correlated with breast cancer prognosis. To make the findings more convincible, we used qRT-PCR to detect the expression levels of LINC00461 and miR-144-3p in breast cancer cells, and conducted western blot to determine KPNA2 protein level. Then, RIP was performed to assess the combination between miR-144-3p and LINC00461 or KPNA2, and dual-luciferase reporter assay was used to validate the targeted relationship between miR-144-3p and KPNA2. Furthermore, Transwell was employed for the examination of cell invasion and migration in breast cancer. Results: LINC00461 was predicted to regulate KPNA2 through sponging miR-144-3p as revealed by the ceRNA network. Besides, LINC00461 and KPNA2 were found to be remarkably highly-expressed in breast cancer cells, while miR-144-3p was poorly-expressed. Silencing LINC00461 could promote miR-144-3p expression, thus inhibiting cell invasion and migration. In addition, KPNA2 was confirmed to be a direct target of miR-144-3p. Silencing miR-144-3p or overexpressing KPNA2 could reverse the inhibitory effect of LINC00461 silencing on cell invasion and migration in breast cancer. Conclusion: LINC00461 promoted the expression of KPNA2 by competitively binding to miR-144-3p, thereby promoting the invasion and migration of breast cancer cells.

ceRNA network development and tumour-infiltrating immune cell analysis of metastatic breast cancer to bone

“…Due to the frequent occurrence of bone metastasis in patients with advanced breast cancer, the understanding of pathogenesis and clinical management of bone metastasis are important and challenging topics in basic research and clinical practice. The ceRNA network, including mRNA, miRNA, and lncRNA, and infiltrating immune cells may be critical to further understand this phenomenon [17] , [18] , [19] , [20] . We observed that tumour samples with bone metastasis had significantly altered proportions of infiltrating cells compared with breast cancer without bone metastasis.…”

“…LncRNA is a type of ncRNA with over 200 nucleotides, which is not related to protein-coding [17] , [18] , [19] , [20] , [21] . New evidence suggests that lncRNA imbalance occurs frequently in many malignant tumours, which is a key factor for carcinogenesis through post-transcriptional regulation and epigenetic modification [22] , [23] .…”

ceRNA Network Development and Tumour-infiltrating Immune Cell Analysis in Metastatic Breast Cancer of Bone

“…Due to the frequent occurrence of bone metastasis in patients with advanced breast cancer, the pathogenesis and clinical management of bone metastasis are important and challenging topics in basic research and clinical practice. The ceRNAs network, including mRNA, miRNA, and lncRNA, and immune cells that in ltrate the tumour may be critical to further understand this phenomenon [12][13][14][15]. We observed that tumour samples with bone metastasis had signi cantly altered proportions of in ltrating cells compared with breast cancer without bone metastasis.…”

“…Lncrna is a type of ncRNA with over 200 nucleotides, which has nothing to do with protein-coding [12][13][14][15][16]. New evidence suggests that lncRNA imbalance occurs frequently in many malignant tumours and are vital for carcinogenesis through post-transcriptional regulation and epigenetic modi cation [17,18].…”

“…Recently, an increasing number of studies show that aberrant lncrnas expression leads to the development of many kinds of malignant tumours, including breast cancer [12][13][14][15][16][17][18]. As a kind of lncrnas, dlx6-as1 is believed to be carcinogenic by regulating the progression of renal cell carcinoma, liver cell carcinoma, glioma, pancreatic cancer and lung adenocarcinoma [19][20][21][22][23][24][25][26].…”