LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis

Abstract

The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.

Long Non-Coding RNAs Associated with Ribosomes in Human Adipose-Derived Stem Cells: From RNAs to Microproteins

“…Similarly, EBLN3P promotes the recovery of impaired spiral ganglion neurons by competitively binding miR-204-5p, regulating TMPRSS3 expression [78]. Despite showing a regulatory function in different cancer types [79,80], here we demonstrated a coding capacity of EBLN3P in hASC, which represents a possible dual-function of this transcript in stem cell biology, including a putative secreted smORF-derived microprotein.…”

Genome-wide screening and immune landscape suggest a potential-m6A-related lncRNA risk signature for predicting prognosis of melanoma

“…Xu et al reported that EBLN3P regulates UHMK1 expression by targeting miR-323a-3p/UHMK1 and accelerates colorectal cancer progression (30). Dai et al demonstrated that EBLN3P accelerates the progression of osteosarcoma by regulating miR-224-5p/Rab10 and is a novel biomarker for the diagnosis and treatment of osteosarcoma (31). However, a literature search showed a limited number of studies reporting the biological mechanisms whereby the remaining pMRlncRNAs affect diseases.…”

EpCAM as a Novel Biomarker for Survivals in Prostate Cancer Patients

“…In particular, based on the miRNA-lncRNA-mRNA co-expression relationship, we discovered that EBLN3P and miR-204-5p strongly correlated with EpCAM were potential to be prognostic biomarkers and therapeutic targets in PCa. Some studies have demonstrated that EBLN3P promotes the progression of liver cancer via alteration of microRNA-144-3p/DOCK4 pathway, and osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis ( Li et al, 2020b ; Dai et al, 2021 ). Unfortunately, no research explores the correlation between prostate cancer and EBLN3P.…”