| Title |
Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line
|
|---|---|
| Published in |
Tumor Biology, August 2015
|
| DOI | 10.1007/s13277-015-3912-2 |
| Pubmed ID | |
| Authors |
Enna Dogra Gupta, Manendra Pachauri, Prahlad Chandra Ghosh, Manchikatla Venkat Rajam |
| Abstract |
The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Unspecified | 6 | 23% |
| Student > Ph. D. Student | 5 | 19% |
| Researcher | 4 | 15% |
| Student > Bachelor | 2 | 8% |
| Student > Master | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 5 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 27% |
| Unspecified | 6 | 23% |
| Agricultural and Biological Sciences | 2 | 8% |
| Veterinary Science and Veterinary Medicine | 1 | 4% |
| Mathematics | 1 | 4% |
| Other | 4 | 15% |
| Unknown | 5 | 19% |
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 19 August 2015.
All research outputs
#15,344,095
of 22,824,164 outputs
Outputs from Tumor Biology
#1,050
of 2,622 outputs
Outputs of similar age
#140,094
of 238,133 outputs
Outputs of similar age from Tumor Biology
#52
of 184 outputs
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So far Altmetric has tracked 2,622 research outputs from this source. They receive a mean Attention Score of 2.2. This one has gotten more attention than average, scoring higher than 53% of its peers.
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We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.