| Title |
Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer
|
|---|---|
| Published in |
Tumor Biology, April 2015
|
| DOI | 10.1007/s13277-015-3152-5 |
| Pubmed ID | |
| Authors |
Rui-Lei Liu, Ye Dong, Yan-Zhen Deng, Wen-Jun Wang, Wei-Dong Li |
| Abstract |
Colorectal cancer (CRC) is one of the most common cancers worldwide. Although chemotherapy is used as a palliative treatment, ultimately, nearly all patients develop drug resistance. Therefore, the cell-inherent DNA repair pathway must reverse the DNA-damaging effect of cytotoxic drugs that mediates therapeutic resistance to chemotherapy. RAD18, a DNA damage-activated E3 ubiquitin ligase, is known to play a critical role in DNA damage repair in cancer cells. Here, we show that RAD18 is highly expressed in human 5-fluorouracil (5-FU)-resistant cancer cells after 5-FU treatment. In addition, RAD18 increases in CRC cells could induce DNA damage repair, suggesting that RAD18 might be a possible target for overcoming drug resistance. Moreover, the expression of tumor suppressor microRNA-145 (miR-145) was negatively correlated with RAD18 expression in CRC tissues of 140 patients. Using luciferase reporters carrying the 3'-untranslated region of RAD18 combined with Western blotting, we identified RAD18 as a direct target of miR-145. Also of interest, suppression of RAD18 by miR-145 enhanced DNA damage in CRC cells after 5-FU treatment. Finally, the 5-FU-resistant cancer cells could be selectively ablated by treatment with miR-145. Taken together, these results suggest that miR-145 can act as an RAD18 inhibitor and contribute as an important factor in reversing drug resistance after chemotherapy. |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 21% |
| Student > Ph. D. Student | 7 | 21% |
| Student > Master | 6 | 18% |
| Lecturer | 2 | 6% |
| Professor > Associate Professor | 2 | 6% |
| Other | 6 | 18% |
| Unknown | 4 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 29% |
| Agricultural and Biological Sciences | 7 | 21% |
| Medicine and Dentistry | 7 | 21% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 9% |
| Psychology | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 5 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 21 December 2021.
All research outputs
#4,682,780
of 22,729,647 outputs
Outputs from Tumor Biology
#157
of 2,622 outputs
Outputs of similar age
#60,333
of 265,144 outputs
Outputs of similar age from Tumor Biology
#5
of 155 outputs
Altmetric has tracked 22,729,647 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,622 research outputs from this source. They receive a mean Attention Score of 2.2. This one has done particularly well, scoring higher than 90% of its peers.
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 265,144 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 155 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.