Original ResearchBasic and Translational—Alimentary TractStrand-Specific miR-28-5p and miR-28-3p Have Distinct Effects in Colorectal Cancer Cells
Section snippets
Colorectal Samples
Eighty-five CRC samples and 26 normal colorectal tissue samples (of which 24 were paired) were collected between 2003 and 2008 at the University Hospital of Ferrara in Ferrara, Italy (first sample set). Forty-two tumors were classified as microsatellite stable (MSS), and 43 tumors were classified as microsatellite unstable (MSI) (Supplementary Methods). For a confirmation set of samples, we obtained 23 paired samples of tumor and adjacent colorectal tissue that were collected between 2002 and
miR-28-5p and miR-28-3p Are Down-regulated in CRC
Expression levels of miR-28-5p and miR-28-3p were analyzed by quantitative real-time polymerase chain reaction (PCR) in 85 human CRC specimens and 26 normal human colorectal specimens. In order to ensure that the reference gene snRNA U6 does not change between normal and tumor samples, we calculated the mean Ct values as 2−Ct. Levels of U6 did not differ between normal and tumor tissue, 2−CtTumor/2−CtNormal = 0.94 (P = .41) (Supplementary Figure 2). Both miRNA-28-5p and miR-28-3p were
Discussion
In the present study, we analyzed 2 independent sets of human CRC samples, for a total of 108 (47 paired with normal tissue), and found significant down-regulation of both mature miR-28 forms. Our study is the first to show down-regulation of miR-28 in cancer. In the literature, only 1 study extensively analyzed miR-28 function in cancer, namely in myeloproliferative neoplasms. Girardot et al identified miR-28 overexpression in platelets of BCR-ABL–negative myeloproliferative neoplasm patients
Acknowledgments
The authors thank Sue Moreau from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript. The authors also thank Dr Thomas Schmittgen from Ohio State University, Columbus OH, and Dr Ramiro Magno and Dr Stan Marée from John Innes Center, United Kingdom, for technical advice on qRT-PCR data analyses.
Drs Nicoloso and Spizzo are currently at the Division of Experimental Oncology, CRO, National Cancer Institute,
References (37)
- et al.
MicroRNA history: discovery, recent applications, and next frontiers
Mutat Res
(2011) - et al.
miR-28 is a thrombopoietin receptor targeting microRNA detected in a fraction of myeloproliferative neoplasm patient platelets
Blood
(2010) - et al.
Micro-RNA profiling in kidney and bladder cancers
Urol Oncol
(2007) - et al.
SnapShot: microRNAs in cancer
Cell
(2009) - et al.
Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion
Biochem Biophys Res Commun
(2011) - et al.
Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis
Gastroenterology
(1996) - et al.
Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression
Mol Cell
(2009) - et al.
Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia
Lab Invest
(2004) - et al.
The Nm23-H1 metastasis suppressor as a translational target
Eur J Cancer
(2010) - et al.
Global cancer statistics
CA Cancer J Clin
(2011)
Cancer statistics, 2010
CA Cancer J Clin
Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia
Proc Natl Acad Sci U S A
Causes and consequences of microRNA dysregulation in cancer
Nat Rev Genet
MicroRNA in colorectal cancer: from benchtop to bedside
Carcinogenesis
Recently identified and potential targets for colon cancer treatment
Future Oncol
miRBase: microRNA sequences, targets and gene nomenclature
Nucleic Acids Res
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments
Clin Chem
RDML: structured language and reporting guidelines for real-time quantitative PCR data
Nucleic Acids Res
Cited by (170)
The importance of hsa-miR-28 in human malignancies
2023, Biomedicine and PharmacotherapySerum MicroRNAs: -28-3p, -31-5p, -378a-3p, and -382-5p as novel potential biomarkers in acute lymphoblastic leukemia
2022, Gene ReportsCitation Excerpt :The miR-28 gene is located at 3q28 and has one of the most commonly altered genes in lymphoid malignancies (Bartolomé-Izquierdo et al., 2017). MiR-28 has increased expression in breast and kidney tumors (Yang et al., 2011) and decreased expression in neoplasms derived from germ cells (Bartolomé-Izquierdo et al., 2017), liver cancer (Shi and Teng, 2015), and colorectal (Almeida et al., 2012). Changes in miR-28 expression in cancers are associated with tumor growth, metastasis, invasion, recurrence, and decreased survival in patients (Almeida et al., 2012; Shi and Teng, 2015; Zhou et al., 2016).
Enhancement of myogenic differentiation and inhibition of rhabdomyosarcoma progression by miR-28-3p and miR-193a-5p regulated by SNAIL
2021, Molecular Therapy Nucleic AcidsCitation Excerpt :Similar to miR-193a-5p, miR-28-3p also exerts effects on tumor proliferation and survival. It inhibits the growth of non-Hodgkin lymphoma35 but, surprisingly, promotes colorectal carcinoma,17 which suggests that it may play a different role in different tumor types. It may also regulate the survival of cardiomyocytes.36
Discovery of novel microRNA mimic repressors of ribosome biogenesis
2024, Nucleic Acids Research
Conflicts of interest The authors disclose no conflicts.
Funding M.I.A. is supported by a PhD fellowship (SFRH/BD/47031/2008) from Fundação para a Ciência e Tecnologia, Portugal. G.A.C. is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust and The University of Texas System Regents Research Scholar. Work in Dr Calin’s laboratory is supported in part by grants from the National Institutes of Health (CA135444), the US Department of Defense, and the Pancreatic Cancer Action Network (2009 Seena Magowitz AACR Pilot Grant). STR DNA fingerprinting was done by the Cancer Center Support grant funded Characterized Cell Line core, NCI # CA16672.