Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma

Abstract

Background LINC00426 is a newly identified long non-coding RNA (lncRNA) with unacknowledged biological roles. Here we set out to characterize the expression status of LINC00426 in osteosarcoma and understand its mechanistic involvement in incidence of doxorubicin (Dox) resistance. Methods The relative expression of LINC00426 and miR-4319 was determined by real-time PCR. Cell viability and proliferation in response to LINC00426 silencing or miR-4319 over-expression was measured with CCK-8 kit and colony formation assay, respectively. The direct association between LINC00426 and miR-4319 was analyzed by pulldown assay with biotin-labelled probes. Results LINC00426 was significantly up-regulated in Dox-resistant osteosarcoma (OS) both in vitro and in vivo, which intimately associated with unfavorable prognosis. SiRNA-mediated knockdown of LINC00426 remarkably compromised cell viability and proliferation in Dox-resistant OS cells, which accompanied with decrease of IC50 and activation of caspase-3. We further predicted and validated the regulatory effects of miR-4319 on LINC00426 expression. Simultaneously, we provided evidences in support of direct binding between LINC00426 and miR-4319 by pulldown assay. Reciprocally negative regulation was observed between LINC00426 and miR-4319 each other. Conclusion Ectopic introduction of miR-4319 significantly surmounted the Dox resistance in OS cells, while miR-4319 inhibition in LINC00426-deficient cells greatly restore this phenotype. We uncovered the important contribution of LINC00426/miR-4319 to Dox resistance in osteosarcoma. Reviewers This article was reviewed by Bo Liang and Sinan Zhu.

Liquid biopsies and cancer omics

“…This has been demonstrated on a mouse model of orthotopic xenografts from a breast tumor, showing a high concentration of miR-1246 in ECVs, and confirmed in vesicles isolated from breast cancer patients, correlating with patients' likelihood of developing recurrencies of the disease 67 . Many other circulating miRNAs and in general noncoding RNAs have been correlated with breast cancer prognosis, miR-34a being significantly downregulated in breast cancer compared to healthy controls [68][69][70][71] .…”

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

“…With the development of bioinformatics technology, the genomics, transcriptome, and epigenomics of cancers were investigated 32 . It was reported that Linc00426 expression level is elevated in doxorubicin resistant osteosarcoma and significantly correlated with unfavorable prognosis 33 . In the present study, we identified Linc00426 highly expressed in LUAD by microarray, suggesting Linc00426 may function as an extensive tumor promoter.…”

Global mapping of cancers: The Cancer Genome Atlas and beyond

“…The huge amount of data generated allowed scientists to paint a broader picture of the mutational status of cancers and helped in both confirming some of the existing data or in generating new biological hypotheses; for example, on cancer‐related genes [ 20 , 21 , 22 ], apoptotic regulators [ 23 , 24 , 25 ], protein stability [ 26 , 27 , 28 , 29 ] and redox regulators [ 30 , 31 , 32 , 33 , 34 , 35 ] or their structural motif [ 36 , 37 ]. TCGA, however, could not inform on large structural variations (SVs) as noncoding regions were not included in the sequencing.…”