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microRNA-451a regulates colorectal cancer proliferation in response to radiation

Overview of attention for article published in BMC Cancer, May 2018
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Title
microRNA-451a regulates colorectal cancer proliferation in response to radiation
Published in
BMC Cancer, May 2018
DOI 10.1186/s12885-018-4370-1
Pubmed ID
Authors

Rebecca Ruhl, Shushan Rana, Katherine Kelley, Cristina Espinosa-Diez, Clayton Hudson, Christian Lanciault, Charles R. Thomas, V. Liana Tsikitis, Sudarshan Anand

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation. In this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student's T-tests for simple comparisons and two-factor ANOVA for evaluating significance. The most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival. Taken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 18%
Student > Ph. D. Student 5 18%
Student > Master 4 14%
Student > Postgraduate 4 14%
Lecturer 2 7%
Other 4 14%
Unknown 4 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 39%
Medicine and Dentistry 6 21%
Veterinary Science and Veterinary Medicine 1 4%
Nursing and Health Professions 1 4%
Computer Science 1 4%
Other 3 11%
Unknown 5 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 May 2018.
All research outputs
#17,948,821
of 23,047,237 outputs
Outputs from BMC Cancer
#5,005
of 8,368 outputs
Outputs of similar age
#236,863
of 326,458 outputs
Outputs of similar age from BMC Cancer
#118
of 204 outputs
Altmetric has tracked 23,047,237 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,368 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,458 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 204 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.