Letter to the Editor

BJC Open article

British Journal of Cancer (2014) 111, 2369–2369. doi:10.1038/bjc.2014.390 www.bjcancer.com
Published online 24 July 2014

Comment on ‘TAp63 suppress metastasis via miR-133b in colon cancer cells’

I Cristobal1, J Madoz-Gurpide2, E Martin-Aparicio2, C Carames1, O Aguilera1, F Rojo2 and J Garcia-Foncillas1

  1. 1Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital Fundacion Jimenez Diaz, E-28040 Madrid, Spain
  2. 2Group of Cancer Biomarkers, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain

Correspondence: Dr J Madoz-Gurpide, E-mail: JMadoz@fjd.es; Professor J Garcia-Foncillas, E-mail: jgfoncillas@gmail.com

We have read with great interest the recently published work by Lin et al (2014), which provides novel relevant findings about the tumour suppressor role of TAp63 via miR-133b downregulation in colorectal cancer (CRC). Of importance, the authors identified miR-133b as a transcriptional target of TAp63, and showed that the modulation of miR-133b expression is essential for the inhibitory effects of TAp63 in CRC cell migration and invasion. Moreover, they showed that TAp63 is expressed at low levels in CRC and proposed this alteration as a potential cause of miR-133b downregulation, which was previously described by our group in CRC cell lines and patient samples (Bandrés et al, 2006). Furthermore, it has been reported that miR-133b has a tumour suppressor role inhibiting cell growth through modulation of the MET signalling pathway (Hu et al, 2010), and it has also been described that low expression level of miR-133b correlates with poor clinical outcome in CRC (Akçakaya et al, 2011).

Notably, although the findings provided by Lin et al (2014) highlight the potential relevance of miR-133b deregulation in CRC progression and metastasis, this issue needs to be fully clarified. A recent publication pointed out that miR-133b contributes to increased CRC cell migration and invasion, and identified CXCR4 as a direct miR-133b target. In that work, Duan et al (2014) analysed 31 CRC patients observing miR-133b downregulation in 29 out of 31 tumour samples, and much lower expression in metastatic tumours. The authors proposed that miR-133b could be having a relevant role in CRC invasion and metastasis. However, only 13 out of the 31 CRC patients had metastatic disease (9 with lymph node metastasis and 4 with liver metastasis). Therefore, further studies confirming the role of miR-133b in the metastatic cohort are warranted.

In this line of thinking, we analysed the potential role of miR-133b in CRC progression and metastasis. We quantified the expression pattern of 377 mature microRNAs using Taqman Low Density Arrays (TLDAs) panel A (Applied Biosystems, Grand Island, NY, USA) in primary and paired metastatic tissues from 17 CRC patients, 12 with liver metastasis and 5 with lung metastasis previously reviewed by a pathologist (FR) to further confirm the diagnosis. All samples were taken anonymously and the ethical committee and institutional review board approved the project. Analysis of relative gene expression data was performed using the 2−ΔCt method and U6B was used as internal control. Downregulation was considered when expression in the metastatic tissue showed at least three-fold decrease compared with its paired primary CRC tissue.

Interestingly, we found miR-133b significantly downregulated in liver metastatic tissues compared with their paired primary CRC tissues (P<0.001). We observed that miR-133b was markedly downregulated in all the 12 CRC liver metastatic tissues analysed. Furthermore, we found lower miR-133b levels in lung metastasis compared with their paired primary CRC tissues although significance was not achieved in this case. In fact, we unexpectedly observed that only two out of the five CRC lung metastatic samples showed miR-133 downregulated and even in one of those cases miR-133b expression was found increased. Moreover, miR-133b showed almost five-fold lower expression levels in liver metastatic tissues compared with lung metastatic tissues.

Altogether, we have confirmed the potential relevance of miR-133b in a larger cohort of CRC patients with liver metastasis and the proposed role for miR-133b in metastatic CRC. In addition, our results would indicate that miR-133b downregulation is more specific of liver CRC metastasis, which indicates that miR-133b might be having a potential role determining the metastatic niche, although further studies are warranted to clarify this issue.

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Conflict of interest

The authors declare no conflict of interest.

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References

  1. Akçakaya P, Ekelund S, Kolosenko I, Caramuta S, Ozata DM, Xie H, Lindforss U, Olivecrona H, Lui WO (2011) MiR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer. Int J Oncol 39: 311–318. | PubMed | ISI |
  2. Bandrés E, Cubedo E, Agirre X, Malumbres R, Zárate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzó M, García-Foncillas J (2006) Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 5: 29. | Article | PubMed | CAS |
  3. Duan FT, Qian F, Fang K, Lin KY, Wang WT, Chen YQ (2014) MiR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression. Mol Cancer 12: 164. | Article |
  4. Hu G, Chen D, Li X, Yang K, Wang H, Wu W (2010) MiR-133b regulates the MET proto-oncogene and inhibits the growth of colorectal cancer cells in vitro and in vivo. Cancer Biol Ther 10: 190–197. | Article | PubMed | ISI |
  5. Lin CW, Li XR, Zhang Y, Hu G, Guo YH, Zhou JY, Du J, Lv L, Gao K, Zhang Y, Deng H (2014) TAp63 suppress metastasis via miR-133b in colon cancer cells. Br J Cancer 110: 2310–2320. | Article | PubMed | ISI |
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Acknowledgements

This study was supported by PI12/01552 and PI13/02609 grants from Instituto de Salud Carlos III FEDER and S2010/BMD2344 grant from the Comunidad de Madrid.

BJC Open article

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