Limits...
The candidate oncogene (MCRS1) promotes the growth of human lung cancer cells via the miR-155-Rb1 pathway.

Liu M, Zhou K, Huang Y, Cao Y - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: However, MCRS1 did not directly bind to these differentially expressed genes.Additionally, we found that the DNA copy number of the MCRS1 gene played a role in MCRS1 overexpression in NSCLCs.Moreover, we put forward the hypothesis that there are regulatory relationships between oncogenes and TSGs apart from the functional synergy of both; the oncogene-miRNA-TSG networks are one of mechanisms among the regulatory relationships; the regulatory relationships and the networks might play active roles in the development and progression of cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. L-M-X101@163.com.

ABSTRACT

Background: Microspherule protein 1 (MCRS1) is a candidate oncogene and participates in various cellular processes, including growth, migration, senescence and transformation. MCRS1 is overexpressed in non-small cell lung cancer (NSCLC) and promotes the growth of cancer cells. However, the mechanisms driving these processes are not fully understood.

Methods: Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in cell lines. Cell proliferation assays and animal experiments were respectively performed to evaluate the growth of NSCLC cells in vitro and in vivo. Microarray analysis was carried out for mRNA profiling. Luciferase reporter assay and microRNA (miRNA) transfection were used to investigate the interaction between miRNA and gene.

Results: Stably knocking down MCRS1 expression inhibited the proliferation of NSCLC cells in vitro and in vivo. By comparing the mRNA expression profiles of NSCLC cells with or without MCRS1 silencing, we found that MCRS1 regulated expressions of various genes related to cell proliferation, including Rb1, TP53, cell cycle-related genes, MYC, E2F2, PCNA, and Ki67. However, MCRS1 did not directly bind to these differentially expressed genes. Here, we confirmed that Rb1, an important tumor suppression gene (TSG), is a direct target of miR-155 which is directly up-regulated by MCRS1. Furthermore, the level of Rb1 expression in NSCLC tissues was inversely correlated with those of miR-155 and MCRS1, and MCRS1 regulated expression of Rb1 via miR-155. Additionally, we found that the DNA copy number of the MCRS1 gene played a role in MCRS1 overexpression in NSCLCs.

Conclusion: MCRS1 overexpression induced NSCLC proliferation through the miR-155-Rb1 pathway and DNA copy-number amplification is one of the mechanisms underlying MCRS1 overexpression in NSCLC. Moreover, we put forward the hypothesis that there are regulatory relationships between oncogenes and TSGs apart from the functional synergy of both; the oncogene-miRNA-TSG networks are one of mechanisms among the regulatory relationships; the regulatory relationships and the networks might play active roles in the development and progression of cancer.

No MeSH data available.


Related in: MedlinePlus

Stably knocking down the expression of MCRS1 inhibited the proliferation of NSCLC cells in vivo and in vitro. a The stable knockdown of MCRS1 expression decreased the levels of MCRS1 mRNA and protein in NSCLC cells compared with those of control cells without the MCRS1 knockdown. b The stable knockdown of MCRS1 expression notably reduced the level of cell viability, as evaluated using an MTT assay. c A diagram of EPLC-32 M1 cells with stably reduced MCRS1 expression and the control cells that were subcutaneously implanted into nude mice. d The stable knockdown of MCRS1 expression significantly suppressed tumor growth in nude mice. The differences between MCRS1 knockdown cells and the matched control cells were analyzed by Student’s t-test (P < 0.05). e Representative images of tumors at five weeks following the subcutaneous implantation of EPLC-32 M1 cells with or without MCRS1 knockdown in nude mice. f The stable knockdown of MCRS1 expression dramatically decreased the tumor weight relative to that of tumors derived from control cells. Msh3: cells with knocked-down MCRS1 expression; Luc: cells without knocked-down MCRS1 expression. *P < 0.05 (Student’s t-test)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4606992&req=5

Fig1: Stably knocking down the expression of MCRS1 inhibited the proliferation of NSCLC cells in vivo and in vitro. a The stable knockdown of MCRS1 expression decreased the levels of MCRS1 mRNA and protein in NSCLC cells compared with those of control cells without the MCRS1 knockdown. b The stable knockdown of MCRS1 expression notably reduced the level of cell viability, as evaluated using an MTT assay. c A diagram of EPLC-32 M1 cells with stably reduced MCRS1 expression and the control cells that were subcutaneously implanted into nude mice. d The stable knockdown of MCRS1 expression significantly suppressed tumor growth in nude mice. The differences between MCRS1 knockdown cells and the matched control cells were analyzed by Student’s t-test (P < 0.05). e Representative images of tumors at five weeks following the subcutaneous implantation of EPLC-32 M1 cells with or without MCRS1 knockdown in nude mice. f The stable knockdown of MCRS1 expression dramatically decreased the tumor weight relative to that of tumors derived from control cells. Msh3: cells with knocked-down MCRS1 expression; Luc: cells without knocked-down MCRS1 expression. *P < 0.05 (Student’s t-test)

Mentions: To investigate the effect of MCRS1 on tumor formation, we stably reduced the level of MCRS1 expression using RNA interference mediated by a retroviral system (pSIREN-RetroQ) in EPLC-32 M1, A549 and 801D cells, representing SCC, AC and LCC cells, respectively. The decreased level of MCRS1 expression was assessed using qRT-PCR and western blotting assays (Fig. 1a).Fig. 1


The candidate oncogene (MCRS1) promotes the growth of human lung cancer cells via the miR-155-Rb1 pathway.

Liu M, Zhou K, Huang Y, Cao Y - J. Exp. Clin. Cancer Res. (2015)

Stably knocking down the expression of MCRS1 inhibited the proliferation of NSCLC cells in vivo and in vitro. a The stable knockdown of MCRS1 expression decreased the levels of MCRS1 mRNA and protein in NSCLC cells compared with those of control cells without the MCRS1 knockdown. b The stable knockdown of MCRS1 expression notably reduced the level of cell viability, as evaluated using an MTT assay. c A diagram of EPLC-32 M1 cells with stably reduced MCRS1 expression and the control cells that were subcutaneously implanted into nude mice. d The stable knockdown of MCRS1 expression significantly suppressed tumor growth in nude mice. The differences between MCRS1 knockdown cells and the matched control cells were analyzed by Student’s t-test (P < 0.05). e Representative images of tumors at five weeks following the subcutaneous implantation of EPLC-32 M1 cells with or without MCRS1 knockdown in nude mice. f The stable knockdown of MCRS1 expression dramatically decreased the tumor weight relative to that of tumors derived from control cells. Msh3: cells with knocked-down MCRS1 expression; Luc: cells without knocked-down MCRS1 expression. *P < 0.05 (Student’s t-test)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4606992&req=5

Fig1: Stably knocking down the expression of MCRS1 inhibited the proliferation of NSCLC cells in vivo and in vitro. a The stable knockdown of MCRS1 expression decreased the levels of MCRS1 mRNA and protein in NSCLC cells compared with those of control cells without the MCRS1 knockdown. b The stable knockdown of MCRS1 expression notably reduced the level of cell viability, as evaluated using an MTT assay. c A diagram of EPLC-32 M1 cells with stably reduced MCRS1 expression and the control cells that were subcutaneously implanted into nude mice. d The stable knockdown of MCRS1 expression significantly suppressed tumor growth in nude mice. The differences between MCRS1 knockdown cells and the matched control cells were analyzed by Student’s t-test (P < 0.05). e Representative images of tumors at five weeks following the subcutaneous implantation of EPLC-32 M1 cells with or without MCRS1 knockdown in nude mice. f The stable knockdown of MCRS1 expression dramatically decreased the tumor weight relative to that of tumors derived from control cells. Msh3: cells with knocked-down MCRS1 expression; Luc: cells without knocked-down MCRS1 expression. *P < 0.05 (Student’s t-test)
Mentions: To investigate the effect of MCRS1 on tumor formation, we stably reduced the level of MCRS1 expression using RNA interference mediated by a retroviral system (pSIREN-RetroQ) in EPLC-32 M1, A549 and 801D cells, representing SCC, AC and LCC cells, respectively. The decreased level of MCRS1 expression was assessed using qRT-PCR and western blotting assays (Fig. 1a).Fig. 1

Bottom Line: However, MCRS1 did not directly bind to these differentially expressed genes.Additionally, we found that the DNA copy number of the MCRS1 gene played a role in MCRS1 overexpression in NSCLCs.Moreover, we put forward the hypothesis that there are regulatory relationships between oncogenes and TSGs apart from the functional synergy of both; the oncogene-miRNA-TSG networks are one of mechanisms among the regulatory relationships; the regulatory relationships and the networks might play active roles in the development and progression of cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. L-M-X101@163.com.

ABSTRACT

Background: Microspherule protein 1 (MCRS1) is a candidate oncogene and participates in various cellular processes, including growth, migration, senescence and transformation. MCRS1 is overexpressed in non-small cell lung cancer (NSCLC) and promotes the growth of cancer cells. However, the mechanisms driving these processes are not fully understood.

Methods: Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in cell lines. Cell proliferation assays and animal experiments were respectively performed to evaluate the growth of NSCLC cells in vitro and in vivo. Microarray analysis was carried out for mRNA profiling. Luciferase reporter assay and microRNA (miRNA) transfection were used to investigate the interaction between miRNA and gene.

Results: Stably knocking down MCRS1 expression inhibited the proliferation of NSCLC cells in vitro and in vivo. By comparing the mRNA expression profiles of NSCLC cells with or without MCRS1 silencing, we found that MCRS1 regulated expressions of various genes related to cell proliferation, including Rb1, TP53, cell cycle-related genes, MYC, E2F2, PCNA, and Ki67. However, MCRS1 did not directly bind to these differentially expressed genes. Here, we confirmed that Rb1, an important tumor suppression gene (TSG), is a direct target of miR-155 which is directly up-regulated by MCRS1. Furthermore, the level of Rb1 expression in NSCLC tissues was inversely correlated with those of miR-155 and MCRS1, and MCRS1 regulated expression of Rb1 via miR-155. Additionally, we found that the DNA copy number of the MCRS1 gene played a role in MCRS1 overexpression in NSCLCs.

Conclusion: MCRS1 overexpression induced NSCLC proliferation through the miR-155-Rb1 pathway and DNA copy-number amplification is one of the mechanisms underlying MCRS1 overexpression in NSCLC. Moreover, we put forward the hypothesis that there are regulatory relationships between oncogenes and TSGs apart from the functional synergy of both; the oncogene-miRNA-TSG networks are one of mechanisms among the regulatory relationships; the regulatory relationships and the networks might play active roles in the development and progression of cancer.

No MeSH data available.


Related in: MedlinePlus