LncRNA PCAT6 promotes tumor progression in osteosarcoma via activation of TGF-β pathway by sponging miR-185-5p

Zhu, Chengdong; Huang, Linhai; Xu, Fei; Li, Ping; Li, Pengfei; Hu, Fangyong

doi:10.1016/j.bbrc.2019.10.136

Cited by 26 publications

(32 citation statements)

References 32 publications

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“…Hence, lncRNAs are potential diagnostic and therapeutic targets for OS. Although numerous lncRNAs are dysregulated in OS, only few lncRNAs have been investigated in detail [34][35][36]. In this study, LINC00514 expression and its clinical relevance in OS were determined.…”

Section: Discussionmentioning

confidence: 99%

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

et al. 2020

Aging

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Long intergenic nonprotein-coding RNA 00514 (LINC00514) is upregulated in papillary thyroid cancer and contributes to its aggressiveness. In this study, we thoroughly explored the expression profile, specific functions, and relevant molecular mechanism of LINC00514 in osteosarcoma (OS). Herein, LINC00514 was significantly upregulated in OS tissues and cells, and increased LINC00514 expression was closely correlated with tumor size, TNM stage, and distant metastasis. OS patients with high LINC00514 expression had shorter overall survival than those with low LINC00514 expression. LINC00514 interference inhibited OS cell proliferation, colony formation, migration, and invasion in vitro but promoted cell apoptosis and G0/G1 cell cycle arrest. LINC00514 downregulation hindered OS tumor growth in vivo. Mechanistically, LINC00514 functioned as a competing endogenous RNA by directly interacting with microRNA-708-5p (miR-708) and consequently increasing the expression of upregulator of cell proliferation (URGCP). Both miR-708 knockdown and URGCP restoration partially neutralized anticancer activities of LINC00514 silencing in OS cells. LINC00514 increases URGCP expression by acting as a competing endogenous RNA for miR-708, thus exerting oncogenic roles in OS progression. In conclusion, the LINC00514/miR-708/URGCP pathway may be a promising target for drug discovery in the future.

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Section: Discussionmentioning

confidence: 99%

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

et al. 2020

Aging

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“…LncRNA PCAT6 was reported to be upregulated in osteosarcoma tissue ( 14 ). The present study detected the expression of lncRNA PCAT6 and MDM2 in osteosarcoma cell lines (hFOB1.19, Saos2, MG63, U2OS and HOS).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, high levels of lncRNA PCAT6 also promoted the proliferation, migration and invasion of non-small cell lung cancer cells and ovarian cancer ( 12 , 13 ). LncRNA PCAT6 was reported to act as a miRNA sponge to regulate the proliferation, migration and invasion of osteosarcoma ( 14 ). However, the effect of lncRNA PCAT6 on the occurrence of osteosarcoma remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA PCAT6 promotes the development of osteosarcoma by increasing MDM2 expression

Guan

Zheng

2020

Oncol Rep

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Osteosarcoma is a severe malignant tumor. Several studies indicated that lncRNA prostate cancer-associated transcript 6 (PCAT6) promoted the development of multiple types of cancers. Studies have also revealed that MDM2 could aggravate tumor symptoms inhibiting P53 expression. However, whether lncRNA PCAT6 could affect the proliferation and metastasis of osteosarcoma cells by regulating P53 expression is unclear. The present study established lncRNA PCAT6-overexpressing osteosarcoma cells. Cell Counting Kit-8, wound healing and Transwell assays were performed to detect the change in proliferation, migration and invasion of these cells, respectively. Subsequently, E3 ubiquitin-protein ligase Mdm2 (MDM2), P53 and P21 expression were determined using western blotting. Finally, MDM2 expression was inhibited and the proliferation, migration and invasion of these cells was determined again. The present study found that the proliferation, migration and invasion of osteosarcoma cells increased following overexpression of lncRNA PCAT6. MDM2 expression was upregulated while the levels of P53 and P21 decreased following overexpression of lncRNA PCAT6. However, the proliferation, migration and invasion of osteosarcoma cells were inhibited following MDM2 knockdown. Additionally, P53 and P21 was rescued following MDM2 knockdown. To conclude, lncRNA PCAT6 promoted the proliferation, migration and invasion of osteosarcoma cells by promoting the expression of MDM2 and suppressing the expression of P53 and P21.

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“…At the transcriptional level, lncRNAs may act as ceRNA by binding several miRNAs and inhibiting their activities (20). For instance, lncRNA prostate cancer associated transcript 6 (PCAT6) promote the progression of osteosarcoma through function as ceRNA of miR-185-5p (21). LncRNA HIF1A antisense RNA 2 (HIF1A-AS2) was identified as ceRNA by sponging miR-33b-5p to facilitate cell survival and migration and modulate the expression of sirtuin 6 (SIRT6) in osteosarcoma (22).…”

Section: Discussionmentioning

confidence: 99%

LncRNA NR_027471 Functions as a ceRNA for miRNA-8055 Leading to Suppression of Osteosarcoma by Regulating the Expression of TP53INP1

et al. 2020

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Osteosarcoma is a malignancy with high aggressiveness and poor prognosis, which occurs mainly in children. The therapeutic strategy against osteosarcoma includes surgery combined with chemotherapy and radiotherapy. Although the treatment of osteosarcoma has been improved in recent years, there is a large proportion of patients with incurable osteosarcoma. Investigation of the mechanism of osteosarcoma progression would be of great help in discovering therapeutic targets for this disease. Long non-coding RNAs play critical roles in the pathogenesis of different types of cancer. The current study showed that long non-coding RNA NR_027471 was downregulated in osteosarcoma cells. In vitro and in vivo studies indicated that upregulation of NR_027471 impeded the viability, proliferation, and invasion of osteosarcoma, as well as induced cell cycle arrest at G1. In addition, binding of miR-8055 to NR_027471 was demonstrated, thereby influencing the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1). Knockdown of NR_027471 promoted epithelial-mesenchymal transition by inhibiting E-cadherin and increasing the expression of zinc finger E-box-binding homeobox 1 (ZEB1), Snail, and fibronectin. These results suggested that overexpression of NR_027471 upregulated TP53INP1 by sponging to miR-8055, leading to suppression of osteosarcoma cell proliferation and progression.

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LncRNA PCAT6 promotes tumor progression in osteosarcoma via activation of TGF-β pathway by sponging miR-185-5p

Cited by 26 publications

References 32 publications

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

Long non‑coding RNA PCAT6 promotes the development of osteosarcoma by increasing MDM2 expression

LncRNA NR_027471 Functions as a ceRNA for miRNA-8055 Leading to Suppression of Osteosarcoma by Regulating the Expression of TP53INP1

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