| Title |
Inhibition of NIPBL enhances the chemosensitivity of non-small-cell lung cancer cells via the DNA damage response and autophagy pathway
|
|---|---|
| Published in |
OncoTargets and therapy, April 2018
|
| DOI | 10.2147/ott.s158655 |
| Pubmed ID | |
| Authors |
Lei Zheng, Huanhuan Zhou, Liwei Guo, Xiaoling Xu, Shengjie Zhang, Weizhen Xu, Weimin Mao |
| Abstract |
Previously, we reported that high expression of nipped-B-like protein (NIPBL) was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer (NSCLC). Moreover, loss of NIPBL decreased lung cancer cells proliferation, migration, invasion and promoted apoptosis as well as sensitivity to chemotherapeutic agents. However, the deep mechanisms were not explored. The objective of this study was to identify the role of NIPBL in DNA damage response, as well as autophagy pathway, so as to interpret the mechanisms of how NIPBL knockdown enhances the chemosensitivity of lung cancer cell. Cells (NCI-H1299 and NCI-H1650) were transfected by specific siRNAs before immunofluorescence and single-cell gel electrophoresis, which were mainly used to observe the differences of DNA damage in different groups. Additionally, protein were obtained and then analyzed by western blot and mass spectroscopy. In this study, we found that knockdown of NIPBL resulted in accumulation of phosphorylated H2AX (γ-H2AX) foci and higher levels of DNA damage, as revealed by comet assay. Western blot assay revealed that loss of NIPBL decreased expression of ATM/ATR, Rad3-related protein and Ku70/Ku80, but increased expression of LC3-B and depletion of p62. Using mass spectroscopy, we identified eight proteins that were significantly differentially expressed upon NIPBL knockdown. Gene Ontology analysis revealed that these proteins are mainly involved in DNA repair, mismatch repair, and binding to damaged DNA. The expression changes in two of the proteins, MSH2 and STAT1, were verified by Western blotting in NIPBL-knockdown cells. In summary, these results reflected that loss of NIPBL impairs the DNA damage response and promotes autophagy. And NIPBL suppression may represent a novel strategy for preventing chemotherapy resistance in lung cancer. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 17% |
| Student > Ph. D. Student | 3 | 17% |
| Other | 1 | 6% |
| Student > Doctoral Student | 1 | 6% |
| Student > Bachelor | 1 | 6% |
| Other | 2 | 11% |
| Unknown | 7 | 39% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 28% |
| Agricultural and Biological Sciences | 2 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
| Unspecified | 1 | 6% |
| Medicine and Dentistry | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 7 | 39% |
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 20 April 2018.
All research outputs
#20,663,600
of 25,382,440 outputs
Outputs from OncoTargets and therapy
#1,597
of 3,016 outputs
Outputs of similar age
#268,557
of 343,807 outputs
Outputs of similar age from OncoTargets and therapy
#63
of 104 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,016 research outputs from this source. They receive a mean Attention Score of 2.9. This one is in the 31st percentile – i.e., 31% 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 343,807 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 104 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.