miR-153 supports colorectal cancer progression via pleiotropic effects that enhance invasion and chemotherapeutic resistance
Authors: Veronika Jenei
Karen Pickard
Marc D Bullock
Graham Packham
John Primrose
John Strefford
Gareth J Thomas
Christos Paraskeva
Richard Mitter
Gavin Kelly
Alex H Mirnezami
Lei Zhang
Amanda Bruce
Journal: Cancer research (2013)
Discipline: CLINICAL MEDICINE
Keywords: microRNAs; miR-153; colorectal cancer; progression; invasiveness
Affiliations: Authors' Affiliations: University of Southampton Cancer Sciences Division, Somers Cancer Research Building; Department of Colorectal Surgery, Southampton University Hospital NHS Trust, Southampton; Bioinformatics Unit, London Research Institute, Cancer Research UK, London; and School of Cellular and Molecular Medicine, University of Bristol, Medical Sciences Building, Bristol, United Kingdom.

Abstract:  Although microRNAs (miRNA) have been broadly studied in cancer, comparatively less is understood about their role in progression. Here we report that miR-153 has a dual role during progression of colorectal cancer by enhancing cellular invasiveness and platinum-based chemotherapy resistance. miRNA profiling revealed that miR-153 was highly expressed in a cellular model of advanced stage colorectal cancer. Its upregulation was also noted in primary human colorectal cancer compared with normal colonic epithelium and in more advanced colorectal cancer stages compared with early stage disease. In colorectal cancer patients followed for 50 months, 21 of 30 patients with high levels of miR-153 had disease progression compared with others in this group with low levels of miR-153. Functional studies revealed that miR-153 upregulation increased colorectal cancer invasiveness and resistance to oxaliplatin and cisplatin both in vitro and in vivo. Mechanistic investigations indicated that miR-153 promoted invasiveness indirectly by inducing matrix metalloprotease enzyme 9 production, whereas drug resistance was mediated directly by inhibiting the Forkhead transcription factor Forkhead box O3a (FOXO3a). In support of the latter finding, we found that levels of miR-153 and FOXO3a were inversely correlated in matched human colorectal cancer specimens. Our findings establish key roles for miR-153 overexpression in colorectal cancer progression, rationalizing therapeutic strategies to target expression of this miRNA for colorectal cancer treatment. 

Retracted: No

PubPeer comments:
 Figure 2F. Much more similar than expected. ![file] , 
 15 April 2022 Editor s Note. https: aacrjournals.org cancerres article 82 8 1669 694343 Editor-s-Note-miR-153-Supports-Colorectal-Cancer The editors are publishing this note to alert readers to a concern about this article (1). In Fig. 2F, we detected that the graph of flow cytometry data for untransfected SW480 cells without cisplatin treatment was duplicated for the miR-153u2013transfected SW480 cells without cisplatin treatment. Reference 1. Zhang L , Pickard K , Jenei V , Bullock MD , Bruce A , Mitter R , et al . miR-153 supports colorectal cancer progression via pleiotropic effects that enhance invasion and chemotherapeutic resistance. Cancer Res 2013;73:6435u201347. ,