LncRNA CBR3-AS1 promotes osteosarcoma progression through the network of miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway

Abstract

Long noncoding RNA (lncRNA) CBR3-AS1 (termed as CBR3-AS1) has been reported to be upregulated in several cancers including osteosarcoma. Its positive impact on the proliferation, migration, and invasion of osteosarcoma cells has been unveiled; nevertheless, whether it also affects the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells is unclear. The purpose for this study was to explore the effects of CBR3-AS1 on the stemness and EMT of osteosarcoma cells as well as its underlying mechanism. qRT-PCR and western blot were applied to detect target gene expression. Function assays were conducted to evaluate the effect of genes on the stemness and EMT of osteosarcoma cells. Mechanism assays were done to verify the association among different genes. In vivo assays were also performed. The obtained data showed that CBR3-AS1 demonstrated a high expression in osteosarcoma cells. CBR3-AS1 could promote stemness and EMT of osteosarcoma cells as well as osteosarcoma tumor growth. Mechanically, CBR3-AS1 sponged miR-140-5p and recruited DDX54 to upregulate NUCKS1, thus activating the mTOR signaling pathway. Furthermore, NUCKS1 could facilitate stemness and EMT of osteosarcoma cells. In summary, this study reveals that CBR3-AS1 exerts an oncogenic role in osteosarcoma through modulating the network of the miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway. Long noncoding RNA (lncRNA) CBR3-AS1 (termed as CBR3-AS1) has been reported to be upregulated in several cancers including osteosarcoma. Its positive impact on the proliferation, migration, and invasion of osteosarcoma cells has been unveiled; nevertheless, whether it also affects the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells is unclear. The purpose for this study was to explore the effects of CBR3-AS1 on the stemness and EMT of osteosarcoma cells as well as its underlying mechanism. qRT-PCR and western blot were applied to detect target gene expression. Function assays were conducted to evaluate the effect of genes on the stemness and EMT of osteosarcoma cells. Mechanism assays were done to verify the association among different genes. In vivo assays were also performed. The obtained data showed that CBR3-AS1 demonstrated a high expression in osteosarcoma cells. CBR3-AS1 could promote stemness and EMT of osteosarcoma cells as well as osteosarcoma tumor growth. Mechanically, CBR3-AS1 sponged miR-140-5p and recruited DDX54 to upregulate NUCKS1, thus activating the mTOR signaling pathway. Furthermore, NUCKS1 could facilitate stemness and EMT of osteosarcoma cells. In summary, this study reveals that CBR3-AS1 exerts an oncogenic role in osteosarcoma through modulating the network of the miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway. IntroductionOsteosarcoma is a kind of malignant tumor that damages the bones, especially the long bones.1Moore D.D. Luu H.H. Osteosarcoma.Cancer Treat. Res. 2014; 162: 65-92Crossref PubMed Scopus (299) Google Scholar It is the top primary bone tumor besetting children and adolescents.2Brown H.K. Tellez-Gabriel M. Heymann D. Cancer stem cells in osteosarcoma.Cancer Lett. 2017; 386: 189-195Crossref PubMed Google Scholar According to a study, in the US, there are 5 osteosarcoma patients among 1,000,000 children aged at or under 19 years.3Anderson M.E. Update on survival in osteosarcoma.Orthop. Clin. North Am. 2016; 47: 283-292Abstract Full Text Full Text PDF PubMed Google Scholar Osteosarcoma is a rare cancer diagnosed at any age,4Sadykova L.R. Ntekim A.I. Muyangwa-Semenova M. Rutland C.S. Jeyapalan J.N. Blatt N. Rizvanov A.A. Epidemiology and risk factors of osteosarcoma.Cancer Invest. 2020; 38: 259-269Crossref PubMed Scopus (63) Google Scholar and it presents a high tendency to metastasize to the lung5Müller D.A. Silvan U. On the biomechanical properties of osteosarcoma cells and their environment.Int. J. Dev. Biol. 2019; 63: 1-8Crossref PubMed Scopus (12) Google Scholar and cause recurrence after therapy.6Cersosimo F. Lonardi S. Bernardini G. Telfer B. Mandelli G.E. Santucci A. Vermi W. Giurisato E. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy.Int. J. Mol. Sci. 2020; 21: 5207Crossref Scopus (53) Google Scholar Although the improvement in treatment methods, including surgery and multidrug chemotherapy, has brought benefits for osteosarcoma patients, the overall survival rate and prognosis are still not optimistic due to its metastasis.2Brown H.K. Tellez-Gabriel M. Heymann D. Cancer stem cells in osteosarcoma.Cancer Lett. 2017; 386: 189-195Crossref PubMed Google Scholar,7Xu R. Feng F. Yu X. Liu Z. Lao L. LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.Cell Prolif. 2018; 51: e12515Crossref PubMed Scopus (85) Google Scholar Therefore, it is essential to explore the pathogenesis as well as the underlying molecular mechanisms of osteosarcoma so as to achieve new breakthrough in the therapy of osteosarcoma.Long noncoding RNAs (lncRNAs) are a category of RNAs characterized by non-protein encoding ability and are over 200 nucleotides in length.8Momen-Heravi F. Bala S. Emerging role of non-coding RNA in oral cancer.Cell Signal. 2018; 42: 134-143Crossref PubMed Scopus (103) Google Scholar Considerable studies have revealed their participation in the development of cancers including osteosarcoma. For instance, lncRNA LET has been reported to be involved in osteosarcoma cell proliferation and invasion.9Kong G. Qi X.J. Wang J.F. Effect of lncRNA LET on proliferation and invasion of osteosarcoma cells.Eur. Rev. Med. Pharmacol. Sci. 2018; 22: 1609-1614PubMed Google Scholar LncRNA GAS5 could suppress cell growth and metastasis of osteosarcoma.10Wang Y. Kong D. LncRNA GAS5 represses osteosarcoma cells growth and metastasis via sponging MiR-203a.Cell Physiol. Biochem. 2018; 45: 844-855Crossref PubMed Scopus (29) Google Scholar,11Fu D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis.Aging. 2019; 11: 8374-8385Crossref PubMed Scopus (79) Google Scholar Moreover, it has been reported that lncRNA CBR3-AS1 could induce the proliferation, migration, and invasion, while repressing the apoptosis of osteosarcoma cells.12Zhang Y. Meng W. Cui LncRNA CBR3-AS1 predicts prognosis and promotes in 2018; PubMed Scopus (29) Google Scholar the impact of CBR3-AS1 on the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells unclear. this study to explore the impact of CBR3-AS1 on stemness and EMT of osteosarcoma to the RNA that lncRNA RNA expression by to has been reported as a for RNAs to in the and development of D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis.Aging. 2019; 11: 8374-8385Crossref PubMed Scopus (79) Google Scholar on the lncRNA could osteosarcoma cell invasion and via modulating the S. F. D. J. Chen J. Y. J. J. Z. regulates invasion and of 2019; PubMed Scopus Google Scholar LncRNA the proliferation, migration, and invasion of osteosarcoma cells through to upregulate B. N. W. D. Wang S. LncRNA osteosarcoma development through of and Physiol. 2019; PubMed Scopus Google Scholar In CBR3-AS1 as the of to upregulate the of cell cancer Y. J. Liu X. L. Long noncoding RNA RNA promotes the of cancer by sponging and 2020; Google Scholar in this to CBR3-AS1 could through a network to on the stemness and EMT of osteosarcoma have been revealed to be in on their including Y. Wang Y. W. X. L. J. F. Z. Wang Y. of long non-coding RNAs and in 2020; PubMed Scopus Google Scholar Moreover, as and have been as to be in cancer through to F. A. M. 2016; PubMed Scopus Google Scholar For lncRNA has been revealed to facilitate cell proliferation, invasion, and in osteosarcoma through to Liu J.F. Y. J. LncRNA cell proliferation, invasion, and in osteosarcoma by to promote PubMed Scopus Google Scholar In lncRNA has been to the of by thus cancer cell Y. to cancer cell Sci. 2020; PubMed Scopus (12) Google Scholar the CBR3-AS1 and is of in this on the of CBR3-AS1 affects the stemness and EMT of osteosarcoma cells via as well as in this study, new for in promotes stemness and EMT of osteosarcoma studies have revealed that on malignant of cancer including osteosarcoma D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis.Aging. 2019; 11: 8374-8385Crossref PubMed Scopus (79) Google L. X. X. F. Liu Y. X. LncRNA osteosarcoma cell proliferation and Mol. Med. 2018; 22: PubMed Scopus Google Scholar conducted a of to the of CBR3-AS1 in osteosarcoma cells. the the expression of CBR3-AS1 in human and human osteosarcoma cell and on the of CBR3-AS1 a expression in osteosarcoma cells in this study in human especially in and cell and cells were involved in the the of CBR3-AS1 was and the data that and were in and cells the were for the Moreover, the of CBR3-AS1 was also via qRT-PCR and in to the of CBR3-AS1 on the of osteosarcoma cell assays were in and cells. The showed that cell proliferation was due to of it could be of the of CBR3-AS1 has been as a of stem cells in Wang Yu W. Zhu Yu L. Liu expression and in 2017; Google Scholar In this study, under different that as CBR3-AS1 was and it CBR3-AS1 expression was upregulated The in and that CBR3-AS1 could facilitate the stemness of osteosarcoma cells. that the of and cells were as the of CBR3-AS1 CBR3-AS1 was of and cells were has that and are to as the of cancer stem L. X. K. D. The role of and cancer stem Mol. Biol. 2018; PubMed Scopus Google B. B. R. Li A. S. J. S. S. G. regulates the stemness via and to in cancer stem cells cancer Res. 2019; PubMed Scopus Google Y. J. The of and 2014; PubMed Scopus Google Scholar Therefore, to explore the of CBR3-AS1 on the stemness of osteosarcoma the of and were via western on the of western CBR3-AS1 could osteosarcoma cell stemness while CBR3-AS1 could the stemness of osteosarcoma cells In the of CBR3-AS1 on EMT of osteosarcoma cells were different the of and cells were in the of and cells due to CBR3-AS1 while after CBR3-AS1 that of CBR3-AS1 the EMT of osteosarcoma of CBR3-AS1 the EMT of cells. blot was also conducted to the of and after or of In the of and expression and the of and expression as CBR3-AS1 was The were obtained CBR3-AS1 was also conducted in vivo The in that CBR3-AS1 tumor growth as the tumor and in were the CBR3-AS1 could promote the of stemness and EMT of osteosarcoma NUCKS1 expression by sponging has that lncRNA is to as at the via to Y. J. The of and 2014; PubMed Scopus Google Scholar explore the underlying of CBR3-AS1 in osteosarcoma conducted in to the of CBR3-AS1 in and cells. in CBR3-AS1 was in of and cells. that CBR3-AS1 as a to the expression of genes. an was to that CBR3-AS1 could be in The of and qRT-PCR after assays that CBR3-AS1 in and CBR3-AS1 could not it was to that CBR3-AS1 its in a on under the of and of CBR3-AS1 in and the of RNA that miR-140-5p in was the among miR-140-5p was to be involved in the and the was from the and CBR3-AS1 on the of miR-140-5p in different the CBR3-AS1 and miR-140-5p was In assays were and the in that CBR3-AS1 could to miR-140-5p through their as the of was while that of the network in this study, on under and to the gene of The that NUCKS1 and were RNA the of miR-140-5p under different were via and the demonstrated that miR-140-5p was to NUCKS1 was According to the of after miR-140-5p the miR-140-5p and NUCKS1 in and cells the of were as The that miR-140-5p could the effect of CBR3-AS1 on NUCKS1 expression miR-140-5p could the of CBR3-AS1 on NUCKS1 expression miR-140-5p could not the effect of CBR3-AS1 on NUCKS1 expression. that there be for CBR3-AS1 to NUCKS1 expression. In CBR3-AS1 could NUCKS1 expression by sponging miR-140-5p in osteosarcoma NUCKS1 expression by sponging The of CBR3-AS1 in and cells was by and The CBR3-AS1 in and was by and qRT-PCR after for CBR3-AS1 were from under the of The expression of in and cells was via qRT-PCR under the of CBR3-AS1 The of in and was via RNA The and miR-140-5p was by RNA assays were to detect the of in and cells miR-140-5p for miR-140-5p were from and The of miR-140-5p to and was via RNA The of miR-140-5p and NUCKS1 was via assays were conducted to detect the expression of NUCKS1 in and cells different and The expression of NUCKS1 was via qRT-PCR after and cells were or the stemness and EMT of osteosarcoma has been reported to facilitate proliferation and invasion of cancer Liu L. Yu NUCKS1 promotes cancer cell by and activating the signaling 2019; PubMed Scopus Google Scholar also to the of NUCKS1 on malignant of osteosarcoma cells. the expression of NUCKS1 in human and human osteosarcoma cell via The that NUCKS1 was in osteosarcoma in and cells to the of NUCKS1 and in and cells was to be high via qRT-PCR and was involved in the study for its explore the of NUCKS1 on the proliferation of osteosarcoma assays were done in and cells. in the cell was due to NUCKS1 and it was of NUCKS1 in and cells were and after NUCKS1 due to NUCKS1 could that NUCKS1 the stemness of osteosarcoma cells On the NUCKS1 promote the stemness of osteosarcoma cells on the of assays were to the stemness of osteosarcoma cells under different The in and the as NUCKS1 the of and while NUCKS1 in the the of and in osteosarcoma cells. The of western blot showed that of NUCKS1 to the of the stemness of and cells was The of NUCKS1 brought the of that the stemness of and cells was from also the of and cells NUCKS1 was or The in that the EMT of osteosarcoma cells was by NUCKS1 as there were cells on the the EMT was due to NUCKS1 cells The of and were and after NUCKS1 was or on the data of western the expression of was while that of and was after NUCKS1 and NUCKS1 to the NUCKS1 could promote osteosarcoma cell EMT In summary, NUCKS1 could promote the stemness and EMT of osteosarcoma the stemness and epithelial-mesenchymal transition of osteosarcoma The of NUCKS1 in human osteosarcoma cell and cell were via and The of and in and cells was by and cell proliferation ability was by under the of expression or of and in and cells under the of NUCKS1 or was via and of was in NUCKS1 was or upregulated in and cells. The expression of were via western blot NUCKS1 was or in and cells. EMT of and cells was through the after NUCKS1 or The expression of were via western blot and cells were or be recruited by CBR3-AS1 to NUCKS1 to the of and that miR-140-5p could not the of CBR3-AS1 on NUCKS1 expression. that for CBR3-AS1 to the expression of the of the to CBR3-AS1 and NUCKS1 were under the of or and were by CBR3-AS1 and NUCKS1 have been in cancer has been to facilitate of J. D. Zhu M. Yu Z. Liu L. M. M. to promote the effect and via the signaling in cell 2019; PubMed Scopus Google C. Liu J. J. L. Wang Y. Z. Y. X. B. Long noncoding RNA by the through Mol. Med. 2019; PubMed Scopus Google Scholar induce Y. W. Liu Y. X. Li X. Z. Wang Y. X. Function of in cancer cells by the J. 2018; PubMed Scopus Google Scholar promotes the of cancer Y. Y. X. Y. L. J. Yu Y. RNA promotes the proliferation and of cancer cells by to 2019; PubMed Scopus Google Scholar and DDX54 is to Y. to cancer cell Sci. 2020; PubMed Scopus (12) Google Scholar the of and DDX54 have not been well in osteosarcoma qRT-PCR and western blot could that the and of genes after CBR3-AS1 and RNA assays were and DDX54 was by in and cells the CBR3-AS1 and assays were and CBR3-AS1 was by qRT-PCR was to evaluate the of DDX54 and in and cells and The demonstrated that DDX54 was by by and and upregulated by Furthermore, the and of NUCKS1 were and after DDX54 or through qRT-PCR and western in DDX54 NUCKS1 and DDX54 could NUCKS1 expression in and cells. DDX54 NUCKS1 to NUCKS1 expression. assays were verify that DDX54 could not NUCKS1 assays were conducted in and cells. The of the was that DDX54 could not to NUCKS1 as in DDX54 was to to NUCKS1 as the of and cells were qRT-PCR was to the expression of The in and that the of NUCKS1 to DDX54 in and cells. In an recruited by could NUCKS1 be recruited by CBR3-AS1 to NUCKS1 and for CBR3-AS1 and NUCKS1 were in The of were by qRT-PCR CBR3-AS1 expression was The of were by western blot after CBR3-AS1 The of CBR3-AS1 to was by RNA The of CBR3-AS1 to DDX54 was via and The of and in and cells was by and The expression of NUCKS1 was by qRT-PCR under the of DDX54 or The of NUCKS1 was by western blot under the of DDX54 or The DDX54 and NUCKS1 was via and The DDX54 and NUCKS1 was by of and The impact of DDX54 on NUCKS1 was via mTOR signaling in osteosarcoma studies have that the mTOR signaling a role in osteosarcoma Wang X. Li Mechanism of the of signaling on the cell proliferation and apoptosis of osteosarcoma cells through Rev. Med. Pharmacol. Sci. 2020; Google Scholar that CBR3-AS1 could the mTOR signaling to the stemness and EMT of osteosarcoma cells. this the of the mTOR signaling and in and cells CBR3-AS1 The western blot that the of and due to CBR3-AS1 and CBR3-AS1 to and CBR3-AS1 could the mTOR signaling pathway. It has also been reported that NUCKS1 could the mTOR signaling to the proliferation of X. M. J. Z. X. Li M. NUCKS1 is a of in and proliferation of cells via the mTOR signaling Physiol. 2019; Scopus (12) Google Scholar study revealed that CBR3-AS1 could upregulate NUCKS1 by modulating miR-140-5p or DDX54 in and cells. NUCKS1 in activating the mTOR signaling pathway. in and the expression of and NUCKS1 by miR-140-5p could be by CBR3-AS1 Moreover, the effect of DDX54 on the could be by NUCKS1 and CBR3-AS1 could the mTOR signaling in osteosarcoma cells by mTOR signaling in osteosarcoma and The of in the mTOR were via western blot CBR3-AS1 expression was or and The expression of mTOR were in and cells miR-140-5p or NUCKS1 via western and blot assays were conducted to the of mTOR in osteosarcoma cells under different or NUCKS1 bone rare still cause high over the Osteosarcoma of the in the and Cancer 2018; PubMed Scopus Google Scholar Osteosarcoma is to be the malignant bone S. osteosarcoma development of a Cancer Res. 2017; PubMed Scopus Google Scholar and has reported that in the and of including R. Feng F. Yu X. Liu Z. Lao L. LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.Cell Prolif. 2018; 51: e12515Crossref PubMed Scopus (85) Google L. X. X. F. Liu Y. X. LncRNA osteosarcoma cell proliferation and Mol. Med. 2018; 22: PubMed Scopus Google M. M. S. M. and growth expression in J. Cancer 2019; PubMed Scopus (12) Google Scholar CBR3-AS1 has been to be in osteosarcoma and as an to promote proliferation, migration, and invasion of osteosarcoma and cell the molecular of CBR3-AS1 has not been well in and the of CBR3-AS1 on the stemness and EMT of osteosarcoma cells have not be In this study, showed the of CBR3-AS1 and the stemness and EMT of osteosarcoma cells as well as the of the Y. Meng W. Cui LncRNA CBR3-AS1 predicts prognosis and promotes in 2018; PubMed Scopus (29) Google Scholar also that CBR3-AS1 was upregulated in osteosarcoma cells. The and in vivo assays that of CBR3-AS1 the stemness and EMT of osteosarcoma cells as well as osteosarcoma tumor growth. On the the stemness and EMT of osteosarcoma cells was as CBR3-AS1 was In summary, CBR3-AS1 was to as an in also the of this gene in of mechanisms that CBR3-AS1 was in the of the that CBR3-AS1 as a to a and the expression of the target the demonstrated that CBR3-AS1 as the of and the network of was different from the by Y. Meng W. Cui LncRNA CBR3-AS1 predicts prognosis and promotes in 2018; PubMed Scopus (29) Google Scholar Moreover, by also that miR-140-5p could the effects of CBR3-AS1 or NUCKS1 and there be to the expression of on NUCKS1 has been reported to an of cancer Liu L. Yu NUCKS1 promotes cancer cell by and activating the signaling 2019; PubMed Scopus Google Scholar the of NUCKS1 in osteosarcoma cells unclear. In this of the study, that NUCKS1 was in and cells. Furthermore, the of assays and western blot that NUCKS1 an oncogenic effect to promote the stemness and EMT of osteosarcoma demonstrated the role in S. Wang B. Y. J. J. Y. NUCKS1 promotes proliferation, invasion and of cell cancer by Res. 2020; PubMed Scopus Google miR-140-5p could not the of CBR3-AS1 mechanisms CBR3-AS1 and According to of molecular is to lncRNA to RNA L. Li G. Y. Lu X. Wang K. S. Chen via of and Res. 2019; 47: PubMed Scopus Google Scholar on the from and of RNA as well as DDX54 was to as an CBR3-AS1 and The that DDX54 could not NUCKS1, was recruited by CBR3-AS1 to NUCKS1 from the study revealed that CBR3-AS1 could the mTOR signaling via the or the this study that CBR3-AS1 an oncogenic role in the of and it could promote stemness and EMT of osteosarcoma cells. In of molecular CBR3-AS1 could the expression of NUCKS1 by to miR-140-5p or on the mTOR signaling pathway. to the of this study, not this for the molecular of osteosarcoma and and human and human osteosarcoma cell and were from the The cells involved in this study were in and at the cells was for to the RNAs were by and a were applied to and their were a qRT-PCR as for lncRNA and while was for qRT-PCR were and as and cell NUCKS1, and as well as their were from and the were also The were cells The cells were in the after and qRT-PCR was to the and miR-140-5p miR-140-5p and were also from cells were and was applied to cell The were The were at a of a and cells were and as cells in the cells were and the was The of were an were from the cells and by The were an and The were and or at their were for at as the and cells on the were and for of the at CBR3-AS1 were the and at was for and the was a was on the The cells were to and the obtained cell were or at the of RNAs were by or were in this was or for at and were the were cell at RNAs or were to qRT-PCR or western or of CBR3-AS1 to or or were or miR-140-5p the cells and were obtained by the The of was and to the for the was applied a the were to the were and the obtained cell were or as well as for The were by western were from the of In vivo were by Cancer of Cancer The were cells were or and for cells different were of The tumor was after the the were from the and the was for was conducted at and data are as of or was for and or for was as in this IntroductionOsteosarcoma is a kind of malignant tumor that damages the bones, especially the long bones.1Moore D.D. Luu H.H. Osteosarcoma.Cancer Treat. Res. 2014; 162: 65-92Crossref PubMed Scopus (299) Google Scholar It is the top primary bone tumor besetting children and adolescents.2Brown H.K. Tellez-Gabriel M. Heymann D. Cancer stem cells in osteosarcoma.Cancer Lett. 2017; 386: 189-195Crossref PubMed Google Scholar According to a study, in the US, there are 5 osteosarcoma patients among 1,000,000 children aged at or under 19 years.3Anderson M.E. Update on survival in osteosarcoma.Orthop. Clin. North Am. 2016; 47: 283-292Abstract Full Text Full Text PDF PubMed Google Scholar Osteosarcoma is a rare cancer diagnosed at any age,4Sadykova L.R. Ntekim A.I. Muyangwa-Semenova M. Rutland C.S. Jeyapalan J.N. Blatt N. Rizvanov A.A. Epidemiology and risk factors of osteosarcoma.Cancer Invest. 2020; 38: 259-269Crossref PubMed Scopus (63) Google Scholar and it presents a high tendency to metastasize to the lung5Müller D.A. Silvan U. On the biomechanical properties of osteosarcoma cells and their environment.Int. J. Dev. Biol. 2019; 63: 1-8Crossref PubMed Scopus (12) Google Scholar and cause recurrence after therapy.6Cersosimo F. Lonardi S. Bernardini G. Telfer B. Mandelli G.E. Santucci A. Vermi W. Giurisato E. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy.Int. J. Mol. Sci. 2020; 21: 5207Crossref Scopus (53) Google Scholar Although the improvement in treatment methods, including surgery and multidrug chemotherapy, has brought benefits for osteosarcoma patients, the overall survival rate and prognosis are still not optimistic due to its metastasis.2Brown H.K. Tellez-Gabriel M. Heymann D. Cancer stem cells in osteosarcoma.Cancer Lett. 2017; 386: 189-195Crossref PubMed Google Scholar,7Xu R. Feng F. Yu X. Liu Z. Lao L. LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.Cell Prolif. 2018; 51: e12515Crossref PubMed Scopus (85) Google Scholar Therefore, it is essential to explore the pathogenesis as well as the underlying molecular mechanisms of osteosarcoma so as to achieve new breakthrough in the therapy of osteosarcoma.Long noncoding RNAs (lncRNAs) are a category of RNAs characterized by non-protein encoding ability and are over 200 nucleotides in length.8Momen-Heravi F. Bala S. Emerging role of non-coding RNA in oral cancer.Cell Signal. 2018; 42: 134-143Crossref PubMed Scopus (103) Google Scholar Considerable studies have revealed their participation in the development of cancers including osteosarcoma. For instance, lncRNA LET has been reported to be involved in osteosarcoma cell proliferation and invasion.9Kong G. Qi X.J. Wang J.F. Effect of lncRNA LET on proliferation and invasion of osteosarcoma cells.Eur. Rev. Med. Pharmacol. Sci. 2018; 22: 1609-1614PubMed Google Scholar LncRNA GAS5 could suppress cell growth and metastasis of osteosarcoma.10Wang Y. Kong D. LncRNA GAS5 represses osteosarcoma cells growth and metastasis via sponging MiR-203a.Cell Physiol. Biochem. 2018; 45: 844-855Crossref PubMed Scopus (29) Google Scholar,11Fu D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis.Aging. 2019; 11: 8374-8385Crossref PubMed Scopus (79) Google Scholar Moreover, it has been reported that lncRNA CBR3-AS1 could induce the proliferation, migration, and invasion, while repressing the apoptosis of osteosarcoma cells.12Zhang Y. Meng W. Cui LncRNA CBR3-AS1 predicts prognosis and promotes in 2018; PubMed Scopus (29) Google Scholar the impact of CBR3-AS1 on the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells unclear. this study to explore the impact of CBR3-AS1 on stemness and EMT of osteosarcoma to the RNA that lncRNA RNA expression by to has been reported as a for RNAs to in the and development of D. Lu C. Qu X. Li P. Chen K. Shan L. Zhu X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis.Aging. 2019; 11: 8374-8385Crossref PubMed Scopus (79) Google Scholar on the lncRNA could osteosarcoma cell invasion and via modulating the S. F. D. J. Chen J. Y. J. J. Z. regulates invasion and of 2019; PubMed Scopus Google Scholar LncRNA the proliferation, migration, and invasion of osteosarcoma cells through to upregulate B. N. W. D. Wang S. LncRNA osteosarcoma development through of and Physiol. 2019; PubMed Scopus Google Scholar In CBR3-AS1 as the of to upregulate the of cell cancer Y. J. Liu X. L. Long noncoding RNA RNA promotes the of cancer by sponging and 2020; Google Scholar in this to CBR3-AS1 could through a network to on the stemness and EMT of osteosarcoma have been revealed to be in on their including Y. Wang Y. W. X. L. J. F. Z. Wang Y. of long non-coding RNAs and in 2020; PubMed Scopus Google Scholar Moreover, as and have been as to be in cancer through to F. A. M. 2016; PubMed Scopus Google Scholar For lncRNA has been revealed to facilitate cell proliferation, invasion, and in osteosarcoma through to Liu J.F. Y. J. LncRNA cell proliferation, invasion, and in osteosarcoma by to promote PubMed Scopus Google Scholar In lncRNA has been to the of by thus cancer cell Y. to cancer cell Sci. 2020; PubMed Scopus (12) Google Scholar the CBR3-AS1 and is of in this on the of CBR3-AS1 affects the stemness and EMT of osteosarcoma cells via as well as in this study, new for in osteosarcoma.

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