Limits...
Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression.

Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T - BMC Cancer (2013)

Bottom Line: The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture.Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143.These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of medical research, Sun Yat-Sen memorial hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

ABSTRACT

Background: Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells.

Methods: A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143.

Results: The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo.

Conclusions: These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.

Show MeSH

Related in: MedlinePlus

The migration of PC-3 sphere cells was gradually enhanced in differentiation.A, The migration capacity of PC-3 sphere cells and adherent cells was analyzed by transwell assays. Five predetermined fields were photographed at 200x magnification, and cells were counted and analyzed with a histogram (31.5 ± 3.5 versus 122.0 ± 12.5, Student’s t test). B, The migration capacity of re-cultured sphere cells on days 1, 2, 3, and 4 was tested by transwell assays. (ANOVA) **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3585861&req=5

Figure 2: The migration of PC-3 sphere cells was gradually enhanced in differentiation.A, The migration capacity of PC-3 sphere cells and adherent cells was analyzed by transwell assays. Five predetermined fields were photographed at 200x magnification, and cells were counted and analyzed with a histogram (31.5 ± 3.5 versus 122.0 ± 12.5, Student’s t test). B, The migration capacity of re-cultured sphere cells on days 1, 2, 3, and 4 was tested by transwell assays. (ANOVA) **p < 0.01.

Mentions: To evaluate the metastatic mechanism of prostate cancer stem cells, we compared the migration capacity of PC-3 spheres and adherent cells with a transwell assay. Interestingly, less PC-3 sphere cells penetrated through the gel-membrane compared with adherent cells (Figure 2A). However, when we digested the sphere cells into single cells for re-adherent culture, the cells gradually showed increased migration capability and reached the level of adherent cells on the fourth day (Figure 2B). These data suggested that prostate cancer stem cells might exhibit lower metastatic ability but generate differentiated cells expressing a highly aggressive phenotype.


Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression.

Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T - BMC Cancer (2013)

The migration of PC-3 sphere cells was gradually enhanced in differentiation.A, The migration capacity of PC-3 sphere cells and adherent cells was analyzed by transwell assays. Five predetermined fields were photographed at 200x magnification, and cells were counted and analyzed with a histogram (31.5 ± 3.5 versus 122.0 ± 12.5, Student’s t test). B, The migration capacity of re-cultured sphere cells on days 1, 2, 3, and 4 was tested by transwell assays. (ANOVA) **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585861&req=5

Figure 2: The migration of PC-3 sphere cells was gradually enhanced in differentiation.A, The migration capacity of PC-3 sphere cells and adherent cells was analyzed by transwell assays. Five predetermined fields were photographed at 200x magnification, and cells were counted and analyzed with a histogram (31.5 ± 3.5 versus 122.0 ± 12.5, Student’s t test). B, The migration capacity of re-cultured sphere cells on days 1, 2, 3, and 4 was tested by transwell assays. (ANOVA) **p < 0.01.
Mentions: To evaluate the metastatic mechanism of prostate cancer stem cells, we compared the migration capacity of PC-3 spheres and adherent cells with a transwell assay. Interestingly, less PC-3 sphere cells penetrated through the gel-membrane compared with adherent cells (Figure 2A). However, when we digested the sphere cells into single cells for re-adherent culture, the cells gradually showed increased migration capability and reached the level of adherent cells on the fourth day (Figure 2B). These data suggested that prostate cancer stem cells might exhibit lower metastatic ability but generate differentiated cells expressing a highly aggressive phenotype.

Bottom Line: The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture.Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143.These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center of medical research, Sun Yat-Sen memorial hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

ABSTRACT

Background: Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells.

Methods: A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143.

Results: The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo.

Conclusions: These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.

Show MeSH
Related in: MedlinePlus