A novel LncRNA PTH-AS upregulates interferon-related DNA damage resistance signature genes and promotes metastasis in human breast cancer xenografts

Long noncoding RNAs (lncRNAs) are important tissue-specific regulators of gene expression, and their dysregulation can induce aberrant gene expression leading to various pathological conditions, including cancer. Although many lncRNAs have been discovered by computational analysis, most of these are as yet unannotated. Herein, we describe the nature and function of a novel lncRNA detected downstream of the human parathyroid hormone (PTH) gene in both extremely rare ectopic PTH-producing retroperitoneal malignant fibrous histiocytoma and parathyroid tumors with PTH overproduction. This novel lncRNA, which we have named “PTH-AS,” has never been registered in a public database, and here, we investigated for the first time its exact locus, length, transcription direction, polyadenylation, and nuclear localization. Microarray and Gene Ontology analyses demonstrated that forced expression of PTH-AS in PTH–nonexpressing human breast cancer T47D cells did not induce the ectopic expression of the nearby PTH gene but did significantly upregulate Janus kinase–signal transducer and activator of transcription pathway–related genes such as cancer-promoting interferon-related DNA damage resistance signature (IRDS) genes. Importantly, we show that PTH-AS expression not only enhanced T47D cell invasion and resistance to the DNA-damaging drug doxorubicin but also promoted lung metastasis rather than tumor growth in a mouse xenograft model. In addition, PTH-AS–expressing T47D tumors showed increased macrophage infiltration that promoted angiogenesis, similar to IRDS-associated cancer characteristics. Although the detailed molecular mechanism remains imperfectly understood, we conclude that PTH-AS may contribute to tumor development, possibly through IRDS gene upregulation. Long noncoding RNAs (lncRNAs) are important tissue-specific regulators of gene expression, and their dysregulation can induce aberrant gene expression leading to various pathological conditions, including cancer. Although many lncRNAs have been discovered by computational analysis, most of these are as yet unannotated. Herein, we describe the nature and function of a novel lncRNA detected downstream of the human parathyroid hormone (PTH) gene in both extremely rare ectopic PTH-producing retroperitoneal malignant fibrous histiocytoma and parathyroid tumors with PTH overproduction. This novel lncRNA, which we have named “PTH-AS,” has never been registered in a public database, and here, we investigated for the first time its exact locus, length, transcription direction, polyadenylation, and nuclear localization. Microarray and Gene Ontology analyses demonstrated that forced expression of PTH-AS in PTH–nonexpressing human breast cancer T47D cells did not induce the ectopic expression of the nearby PTH gene but did significantly upregulate Janus kinase–signal transducer and activator of transcription pathway–related genes such as cancer-promoting interferon-related DNA damage resistance signature (IRDS) genes. Importantly, we show that PTH-AS expression not only enhanced T47D cell invasion and resistance to the DNA-damaging drug doxorubicin but also promoted lung metastasis rather than tumor growth in a mouse xenograft model. In addition, PTH-AS–expressing T47D tumors showed increased macrophage infiltration that promoted angiogenesis, similar to IRDS-associated cancer characteristics. Although the detailed molecular mechanism remains imperfectly understood, we conclude that PTH-AS may contribute to tumor development, possibly through IRDS gene upregulation. Noncoding RNAs longer than 200 nucleotides are classified as long coding RNAs (lncRNAs), and the current release of the public database LNCipedia contains about 128,000 transcripts and about 57,000 genes (1Volders P.J. Anckaert J. Verheggen K. Nuytens J. Martens L. Mestdagh P. et al.Lncipedia 5: towards a reference set of human long non-coding rnas.Nucl. Acids Res. 2019; 47: D135-D139Crossref PubMed Scopus (221) Google Scholar). Recent studies have shown that lncRNAs regulate tissue-specific gene expression through interaction with DNA, proteins, and RNA, thereby driving vital processes, such as differentiation, development, and immunoregulation (2Batista P.J. Chang H.Y. Long noncoding RNAs: cellular address codes in development and disease.Cell. 2013; 152: 1298-1307Abstract Full Text Full Text PDF PubMed Scopus (1880) Google Scholar, 3Fatica A. Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development.Nat. Rev. Genet. 2014; 15: 7-21Crossref PubMed Scopus (2132) Google Scholar, 4Hitachi K. Nakatani M. Takasaki A. Ouchi Y. Uezumi A. Ageta H. et al.Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation.EMBO Rep. 2019; 20e47468Crossref PubMed Scopus (32) Google Scholar, 5Chen Y.G. Satpathy A.T. Chang H.Y. Gene regulation in the immune system by long noncoding RNAs.Nat. Immunol. 2017; 18: 962-972Crossref PubMed Scopus (397) Google Scholar). Usually, lncRNA expression is tightly controlled and fine tuned, but dysregulation causes a variety of diseases, including cancer. In fact, next-generation sequencing transcriptomes have revealed that thousands of lncRNAs are abnormally expressed in various cancers (6Huarte M. The emerging role of lncRNAs in cancer.Nat. Med. 2015; 21: 1253-1261Crossref PubMed Scopus (1766) Google Scholar, 7Schmitt A.M. Chang H.Y. Long noncoding RNAs in cancer pathways.Cancer Cell. 2016; 29: 452-463Abstract Full Text Full Text PDF PubMed Scopus (2034) Google Scholar, 8Liu Z. Chen Z. Fan R. Jiang B. Chen X. Chen Q. et al.Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.Mol. Cancer. 2017; 16: 1-9Crossref PubMed Scopus (120) Google Scholar, 9Zhou W. Ye X. Xu J. Cao M.-G. Fang Z.-Y. Li L.-Y. et al.The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b.Sci. Signal. 2017; 10eaak9557Crossref Scopus (137) Google Scholar, 10He S.-W. Xu C. Li Y.-Q. Li Y.-Q. Zhao Y. Zhang P.-P. et al.AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma.Oncogene. 2020; 39: 5616-5632Crossref PubMed Scopus (14) Google Scholar). Some lncRNAs affect cancer phenotypes and promote ultimately catastrophic metastasis (7Schmitt A.M. Chang H.Y. Long noncoding RNAs in cancer pathways.Cancer Cell. 2016; 29: 452-463Abstract Full Text Full Text PDF PubMed Scopus (2034) Google Scholar, 8Liu Z. Chen Z. Fan R. Jiang B. Chen X. Chen Q. et al.Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.Mol. Cancer. 2017; 16: 1-9Crossref PubMed Scopus (120) Google Scholar, 9Zhou W. Ye X. Xu J. Cao M.-G. Fang Z.-Y. Li L.-Y. et al.The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b.Sci. Signal. 2017; 10eaak9557Crossref Scopus (137) Google Scholar, 10He S.-W. Xu C. Li Y.-Q. Li Y.-Q. Zhao Y. Zhang P.-P. et al.AR-induced long non-coding RNA LINC01503 facilitates proliferation and metastasis via the SFPQ-FOSL1 axis in nasopharyngeal carcinoma.Oncogene. 2020; 39: 5616-5632Crossref PubMed Scopus (14) Google Scholar). While lncRNAs are receiving increased attention, most are predicted only by computational analysis and very are H. C. P. to and long noncoding RNAs: and Genet. Scholar). is not only in the of lncRNAs but also in their cellular and the of a new lncRNA downstream of the human parathyroid hormone (PTH) gene in ectopic PTH-producing malignant fibrous histiocytoma K. Y. H. M. K. et of of and a novel lncRNA the PTH gene ectopic PTH-producing 2017; PubMed Scopus Google Scholar). the lncRNA also detected in a parathyroid that its expression is to the expression of the nearby PTH the exact and function of the lncRNA not Herein, we describe the of lncRNA and the of forced expression PTH–nonexpressing human breast cancer T47D cells gene expression including the PTH gene by Gene Ontology analysis, the of expression of the lncRNA cell cancer are demonstrated in and in In the lncRNA of as lncRNA, which we named is the downstream of the PTH PTH-AS expression in T47D cells did not induce PTH expression but transducer and activator of transcription and its downstream interferon-related DNA damage resistance signature The IRDS genes to a of genes and and Janus IRDS expression is via the rather than the K. M. B. The and the of in 2017; PubMed Scopus Google Scholar, B. role in the tumor resistance to and Res. 18: PubMed Scopus Google Scholar). IRDS is with resistance to and with DNA-damaging including doxorubicin and resistance to DNA the expression of IRDS in tumor with and has as a for the and of various including breast cancer H. et interferon-related gene signature for DNA damage resistance is a for and for breast A. PubMed Scopus Google Scholar, A. C. W. of transducer and activator of transcription in breast Res. Google Scholar). In addition, the detailed mechanism has not been IRDS in the tumor both tumor cells and and IRDS tumor in to drug The of revealed that PTH-AS expression in T47D cells enhanced and resistance to similar to the for In a mouse xenograft PTH-AS expression promoted lung rather than T47D tumor growth and increased macrophage infiltration and that PTH-AS is in malignant and drug novel lncRNA discovered in ectopic PTH-producing and with PTH downstream of the PTH gene that the only with the rather than the that the lncRNA of in the the lncRNA in the to human In addition, and of DNA the exact and of lncRNA transcripts and transcripts with and and The of these transcripts are to transcription a novel lncRNA in the which is the of the PTH and we named to to long non-coding RNA gene 2014; PubMed Scopus Google Scholar). we investigated the which is a to lncRNA The of PTH-AS in nuclear and RNA by shown in of PTH-AS in the only in the that PTH-AS is in the In addition, transcription with of in of the that PTH-AS PTH-AS expression detected in with PTH in to ectopic PTH-producing but not in PTH–nonexpressing cell including cancers that PTH-AS expressed only in tumors we that PTH-AS in the regulation of PTH are PTH-producing cell we to the of PTH-AS PTH expression cells that not expression the PTH-AS coding PTH–nonexpressing human breast cancer T47D cells to PTH expression not with PTH–nonexpressing cells such as human breast cancer and human lung cancer that PTH-AS expression not induce ectopic PTH gene expression in In the of lncRNAs contribute to and RNA and are in gene regulation in a variety of (2Batista P.J. Chang H.Y. Long noncoding RNAs: cellular address codes in development and disease.Cell. 2013; 152: 1298-1307Abstract Full Text Full Text PDF PubMed Scopus (1880) Google Scholar, W. The and of long non-coding Rev. PubMed Scopus Google Scholar, Y. Chen of long noncoding RNAs.Nat. 2019; 21: PubMed Scopus Google Scholar). we T47D cells that PTH-AS and the of PTH-AS gene the the PTH-AS gene did not the of the for we that are longer than the by and The the of the PTH-AS transcripts may we to a of the of the PTH-AS transcription as a for to the we that is similar in to the gene analysis T47D cells PTH-AS in to PTH-AS–expressing cells to the genes differentially expressed in with genes expression in cells PTH-AS expression in T47D cells genes and genes analysis the public classified many of the genes as including and via as as by revealed that these with the immune In addition, such as and as molecular as as such as in and which are as of and and Gene set analysis also a PTH-AS expression and these the database transcription in Acids Res. PubMed Scopus Google and as transcription that to the of genes expression significantly by PTH-AS expression in T47D cells In fact, analysis showed the expression of and as as their in cells than in and cells In the expression of such as and which to the cancer-promoting increased the expression of PTH-AS and we and cells to PTH-AS expression and analysis revealed that and IRDS gene expression in T47D cells increased with PTH-AS but with PTH-AS and PTH-AS and in and cells also a PTH-AS and IRDS expression and that PTH-AS is in the regulation of and its downstream IRDS expression and that is not to IRDS expression is via the rather than the H. et interferon-related gene signature for DNA damage resistance is a for and for breast A. PubMed Scopus Google Scholar). analysis showed that increased with PTH-AS expression in T47D cells and showed a similar to but the not by PTH-AS expression, that not by PTH-AS expression PTH-AS expression may in IRDS expression through increased of rather than of IRDS can promote tumor by cancer cells to and resistance to DNA-damaging B. role in the tumor resistance to and Res. 18: PubMed Scopus Google Scholar, H. et interferon-related gene signature for DNA damage resistance is a for and for breast A. PubMed Scopus Google Scholar, tumor and the in cancer the a and PubMed Scopus Google Scholar, H. and their genes in the tumor 2014; PubMed Scopus Google Scholar). we investigated the expression of which the malignant of cancer of PTH-AS expression the proliferation of T47D cells with the DNA-damaging PTH-AS expression in T47D cells did not affect cell but did to a drug resistance and the EMT expression only the showed a with PTH-AS expression and The of T47D cells showed with PTH-AS expression but to and the of PTH-AS expression the and invasion of T47D cells The showed that the by the not by PTH-AS expression but and and invasion significantly promoted and expression, which is with very in cells and did not with PTH-AS expression The analysis showed expression of genes to and with PTH-AS expression in T47D cells that PTH-AS expression T47D cell but in showed of PTH-AS expression PTH-AS expression did not affect but enhanced DNA damage as as and In addition, of in cells and in expression of IRDS genes and with these gene expression the of resistance and invasion by cells in cells and cells as as T47D cells that PTH-AS expression in T47D and cells the expression of various genes and cancer via of we the of PTH-AS and malignant progression of T47D cells in cells with PTH-AS expression and tumor growth in tumor growth and tumor and of the cell showed significantly in tumors PTH-AS–expressing that PTH-AS expression promoted tumor and also increased tumor may to enhanced Although the lung of detected in of the PTH-AS–expressing tumors with these the of human to mouse in lung significantly in with PTH-AS–expressing tumors In human breast cancer T47D xenograft in of the PTH-AS expression in the but lung detected in with PTH-AS–expressing tumors that PTH-AS expression in T47D cells did not affect tumor and growth but did promote tumor and lung also shown by cells and cells with various PTH-AS expression and we the of PTH-AS expression in cancer cells the tumor PTH-AS expression tumor cells in with PTH-AS expression of human and cells PTH-AS–expressing tumors also showed expression of a of IRDS genes Recent have demonstrated that in breast cancer are with macrophage infiltration and P. P. H. R. Z. et but not its are with macrophage infiltration and in breast Cancer. 2014; PubMed Scopus Google Scholar). with analysis the macrophage revealed that in PTH-AS–expressing tumors with expression and in tumor as as tumor cells are the of growth and induce tumor expression and PTH-AS expression in cells In the expression of human cells very and not by PTH-AS In mouse and significantly increased in tumors with PTH-AS expression and that by tumor rather than tumor is in in of PTH-AS expression in T47D tumors macrophage and in and tumor infiltration of with and the of cells The with PTH-AS expression in T47D cells in cells with and The in the and in the tumor by and of PTH-AS expression T47D cells of macrophage mouse macrophage cells and of T47D cells with PTH-AS expression the cells in a and the of cells and macrophage to the of and the of cells by the as and expression of in The expression of gene by RNA the tumor The expression of the are shown in to human and are shown as the and by not parathyroid transducer and activator of transcription we investigated the in with PTH-AS Microarray and showed that PTH-AS expression in T47D cells increased the gene expression of a that promotes macrophage is to of the genes I. M. The regulation of by and their 2013; PubMed Google and that the increased expression of in cells by analysis revealed that the in the in T47D cells with PTH-AS expression than in with PTH-AS expression in T47D tumors with PTH-AS expression also a mouse macrophage cells to T47D cells with PTH-AS expression promote macrophage infiltration via The showed that of cells promoted by the of cells with PTH-AS expression and and by the of and In addition, is with A. A. P. A. M. The system in of macrophage and Immunol. Full Text Full Text PDF PubMed Scopus Google Scholar). to analysis, the expression of mouse macrophage such as and increased in tumors with PTH-AS expression but the expression of such as and not PTH-AS expression may expression downstream of and contribute to macrophage tumors and in the of the lncRNAs have have been shown to in important and various Recent in have to the of new but their are The of to the nature and function of the novel lncRNA downstream of the PTH gene detected in ectopic PTH-producing Herein, we demonstrated that the lncRNA of in is lncRNA by the in the downstream of the PTH and we named but expression of PTH-AS in PTH–nonexpressing T47D breast cancer cells did not induce PTH expression and and its downstream IRDS genes. In and in analyses revealed that PTH-AS expression increased the malignant of cancer cells and promoted metastasis but not tumor In addition, showed that PTH-AS cancer with the expression of various including through upregulation. In T47D with PTH-AS expression, the expression of the gene for such as a in the expression of the cancer-promoting with the K. M. B. The and the of in 2017; PubMed Scopus Google Scholar, B. role in the tumor resistance to and Res. 18: PubMed Scopus Google Scholar, H. and their genes in the tumor 2014; PubMed Scopus Google Scholar). In to EMT and IRDS expression in cancer cells is with resistance to DNA damage by and H. et interferon-related gene signature for DNA damage resistance is a for and for breast A. PubMed Scopus Google Scholar). PTH-AS–expressing T47D cells showed resistance to the DNA-damaging drug that PTH-AS has to contribute to through IRDS upregulation. IRDS expression in a variety of cancer including breast with resistance to and and are to as for and H. et interferon-related gene signature for DNA damage resistance is a for and for breast A. PubMed Scopus Google Scholar). which IRDS expression, may also a in various cancers is IRDS also can metastasis and by and through in tumor tumor and the in cancer the a and PubMed Scopus Google Scholar, H. and their genes in the tumor 2014; PubMed Scopus Google Scholar). In xenograft PTH-AS expression did not affect tumor growth but lung In addition, PTH-AS–expressing T47D tumors significantly increased infiltration and possibly mouse with tumor the increased infiltration in tumors with PTH-AS expression, is that the increased expression of which is the gene of is In fact, in that cells with PTH-AS expression promote of mouse In addition, tumors with PTH-AS expression to the and which is with the to a of in has been and has been that also promote malignant progression in various including breast cancer M. Y. M. L. R. et and by only of their in breast Rep. 2020; PubMed Scopus Google Scholar). these PTH-AS expression in tumor cells may induce infiltration and through increased a tumor to malignant not PTH-AS investigated the expression of in expression but with PTH-AS expression not to PTH-AS expression via have been of nuclear lncRNAs in the expression of H. C. Z. Chen Li L. C. to cancer progression via Res. 2020; 39: PubMed Scopus Google Scholar, L. A. M. of human coding and noncoding genes through RNA 2017; PubMed Scopus Google Scholar). lncRNAs that regulate gene expression as of the Y. Chen of long noncoding RNAs.Nat. 2019; 21: PubMed Scopus Google Scholar, Long non-coding RNAs: of nuclear and 2014; PubMed Scopus Google the to the and expression through interaction with I. A. L. et al.The lncRNA human cell by of A. 2020; PubMed Scopus Google Scholar). This that in the of lncRNAs such as its mechanism of expression to both and many lncRNAs have been that promote tumor in a variety of cancers through the of The in long noncoding 2019; PubMed Scopus Google Scholar, P. Y. M. Y. X. et role of by lncRNA and Cancer. 2020; PubMed Scopus Google Scholar, J. H. Jiang W. L. and Scopus Google Scholar). that PTH-AS is in the lncRNAs have transcripts A. lncRNA and Google but these not the that PTH-AS The coding of lncRNA can investigated to by and analysis, as as of and P. Y. M. Y. X. et role of by lncRNA and Cancer. 2020; PubMed Scopus Google Scholar). the the PTH-AS these are to have coding of the of and with and the to In fact, that lncRNAs such as and H19 have coding for these The of the H19 gene may function as Cell. PubMed Scopus Google Scholar, A. P.J. et al.The of the mouse gene is a and in the Full Text PDF PubMed Scopus Google Scholar, M. of non-coding PubMed Scopus Google Scholar). that PTH-AS has coding is a computational may to by is to the of the PTH-AS function the of tissue-specific gene expression, and regulate the expression of genes in W. The and of long non-coding Rev. PubMed Scopus Google Scholar, gene regulation by long J. 2015; 16: PubMed Scopus Google Scholar, B. A. R. Chen Y. et long noncoding RNA to gene PubMed Scopus Google Scholar, R. of the non-coding RNA expression and 2016; PubMed Scopus Google Scholar, Chen J. M. et regulation of gene expression by lncRNA transcription and 2016; PubMed Scopus Google Scholar, P. Y. R. et lncRNA its Cell. 2016; Full Text Full Text PDF PubMed Scopus Google Scholar, J. et a lncRNA a gene 2017; PubMed Scopus Google Scholar). we that PTH-AS of the of the expression of the nearby PTH and that its expression in PTH–nonexpressing cells the parathyroid of PTH in the of PTH the mechanism by which the PTH gene is expressed in a remains This is in a to the in the which is a of PTH parathyroid a novel gene Full Text PDF PubMed Scopus Google Scholar). The gene is in a the of tissue-specific expression, in of in PubMed Scopus Google Scholar, its regulation of and development, and role in Rev. 2016; PubMed Scopus Google Scholar). In ectopic PTH-producing tumors have been in only a including the we K. R. H. M. M. et of parathyroid hormone by cell lung cancer in a with PubMed Scopus Google Scholar, A. and ectopic of parathyroid hormone by with of the gene for parathyroid J. Med. PubMed Scopus Google Scholar, A. A. B. A. a parathyroid Med. PubMed Scopus Google Scholar, R. a parathyroid by Full Text Full Text PDF PubMed Scopus Google Scholar, J. A. et of to ectopic of the parathyroid hormone PubMed Scopus Google Scholar, M. Y. A. et of parathyroid hormone in a with J. PubMed Scopus (14) Google Scholar, P. P. of parathyroid hormone in a a and of the J. Med. Google Scholar, Y. H. Y. Y. M. with parathyroid a Med. PubMed Scopus Google Scholar, K. M. Y. M. et with gastric parathyroid a and of the J. 2013; PubMed Scopus Google Scholar, R. K. P.J. with of the Full Text PDF PubMed Scopus Google Scholar, of parathyroid hormone by a malignant tumor in a PubMed Scopus Google Scholar, R. L. A. as a of ectopic PubMed Scopus Google Scholar, M. L. K. of parathyroid hormone by a cell lung in and in Google Scholar, K. A. et cancer with by parathyroid hormone and parathyroid Full Text PDF PubMed Scopus Google Scholar, and in a with cell for parathyroid Full Text Full Text PDF PubMed Google Scholar, K. A. K. H. et cell with parathyroid J. PubMed Scopus Google Scholar, H. A. A. B. Y. by parathyroid hormone in a with a PubMed Scopus Google Scholar). This may the of PTH to cells did not PTH by forced expression of we that PTH-AS expression induce PTH expression, in these that PTH-AS may regulate PTH expression only in with in such as and which we may regulators of ectopic PTH K. Y. H. M. K. et of of and a novel lncRNA the PTH gene ectopic PTH-producing 2017; PubMed Scopus Google Scholar). to expression of lncRNA is of aberrant Y. C. R. A. et and genes are in PubMed Scopus Google Scholar). with is to in the expression of have been detected in ectopic PTH-producing tumors with PTH-AS expression K. Y. H. M. K. et of of and a novel lncRNA the PTH gene ectopic PTH-producing 2017; PubMed Scopus Google Scholar). the expression of various genes through both and J. H. Li J. R. Y. et in and transcription in human cancer 2020; PubMed Scopus Google which may a of PTH-AS In human breast cancer T47D cells to of the of PTH-AS detected in with ectopic PTH-producing may in the development of and in than parathyroid cells cell conditions, to et C. et of cells human 2020; 1-9Crossref Scopus Google demonstrated that can parathyroid new function of PTH-AS to progression may In revealed a of the and of a novel lncRNA that we discovered in ectopic PTH-producing Although the exact molecular mechanism has not yet been that PTH-AS expression in T47D cells and its downstream cancer-promoting IRDS and in enhanced tumor is to lncRNA expression in cancer cell that not In the is to the expression of PTH-AS in malignant tumors and its breast cancer T47D cells and cells and human lung cancer cells cells in and with and RNA cells by the the of RNA of for transcription than to with and Gene expression to by the for and and for is detailed in and tumors in the the to a to and to a a with and with the as shown in detected by the and by analysis of the and of the to the In RNA by by and to the and in The and their by The RNA to the to and nuclear In H19 and as for and nuclear RNA for the of RNA the the Gene Microarray The The and The and by the for the expression than than with the as and these analysis and the public and with and with in the cells with by as detailed in nuclear with the a by a cell by cells in a and and the of the of and invasion the In the invasion the with in in the of a and the with of cells that through the with and with and the of cells and mouse macrophage to a of cells in of and the the in and cell with of in the the cells with and with the and cells and mouse in tumor and to the The cell cells a in of for The tumor by with of of tumor also in the the in and tumor to cell and PTH-AS expression by to and In addition, the by of expression and which to have the The for is as and including a variety of cells to the by with and expression by the is shown in of in PTH-AS–expressing cells The the cells of to the of cells by to have expression and in various by by cells in a and with various of of to the cells during the of in and the a studies in with for and The by the cells in the axis and axis of the tumors with a to the the tumor and the tumor as tumors in and lung by by This with analysis and can human cells in a mouse xenograft with P. is and of xenograft metastasis 2020; Full Text Full Text PDF PubMed Scopus Google Scholar). RNA mouse lung the and as human mouse the human expression to the mouse expression and as the of human cells in mouse lung the with and with with and and with by nuclear a lung to the the to for the with to a in cells with various human and as a of cells and to the and by analysis and are expressed as the to to the by Some of the in have been in for PTH-AS is the for with and The in are also the Gene with to the of are the This contains The that have of with the of M. A. M. A. and H. H. M. A. M. and H. H. M. and M. M. A. M. H. and M. M. A. This by the for the of to and M.

Hali tarjima qilinmagan