RETRACTED ARTICLE: LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis

Abstract

Dysregulation of non-coding RNAs, including miRNAs and lncRNAs has been reported to play vital roles in gastric cancer (GC) carcinogenesis, but the mechanism involved is largely unknown. Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved. MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo, whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity. Furthermore, we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC. Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation. Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC. Finally, high expression of LINC01410, along with low expression of miR-532-5p, was associated with poor survival outcome in GC patients. Our studies uncover a mechanism for constitutive LINC1410-miR-532-5p-NCF2-NF-κB feedback loop activation in GC, and consequently, as a potential therapeutic target in GC treatment.

<p>LINC01410 Knockdown Suppresses Cervical Cancer Growth and Invasion via Targeting miR-2467-3p/VOPP1 Axis</p>

“…28 At first, LINC01410 was reported to enhance gastric cancer metastasis. 20 Afterwards, a study shows that LINC01410 increases growth and invasiveness of colon cancer cells through sponging miR-3128. 21 Recently, a work reveals a close correlation between LINC01410 expression and thyroid cancer development.…”

“…LINC01410 has been found to promote gastric cancer development, enhance colon cancer growth and regulate thyroid cancer apoptosis. [20][21][22] However, the role of LINC01410 in CC remains undetermined. Here we found that LINC01410 was upregulated in CC samples.…”

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

“…Accumulating evidence has shown that lncRNAs play vital roles in multiple biological processes including proliferation, apoptosis, angiogenesis, drug resistance, and metastasis in various malignant tumors. [34][35][36][37][38] MALAT1 is a highly conserved lncRNA that was originally identified and is highly expressed in non-small-cell lung cancer. 39 MALAT1 presented diverse regulative functions on multiple malignant tumors including OS.…”

Ezrin promotes breast cancer progression by modulating AKT signals

“…Given that angiogenesis is crucial for the metastasis and progression of cancer, 24,25 we explored whether Ezrin has a role in BC angiogenesis. By performing vasculogenic mimicry and microtubule formation assay, we detected that the vascular mimicry and microtubule formation ability of HUVECs were reduced in the Ezrin depletion cells, but increased in the Ezrin overexpressed cells (Fig.…”