Related Experiment Video
Updated: Mar 21, 2026
06:44
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
4.7K
B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu
Zhang Zhang Sun1, Ting Zhang2, Kuan Ning1
1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
Oncology Reports
|May 14, 2016
Summary
B7-H3 overexpression increases BRCC3 expression, leading to 5-fluorouracil (5-Fu) resistance in colorectal cancer by enhancing DNA repair. Targeting BRCC3 may improve 5-Fu efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- 5-fluorouracil (5-Fu) is a primary colorectal cancer chemotherapy, yet its response rate is below 50%.
- B7-H3, an immunoglobulin linked to metastasis and poor prognosis, is upregulated in tumors.
- BRCC3, part of the DNA repair complex, shows a relationship with B7-H3.
Purpose of the Study:
- To investigate the functional relationship between B7-H3 and BRCC3 in colorectal cancer.
- To explore the role of BRCC3 in B7-H3-mediated 5-fluorouracil resistance.
Main Methods:
- Real-time PCR and western blot analysis to assess BRCC3 expression.
- B7-H3 overexpression and knockdown in SW480 and HCT-8 colorectal cancer cell lines.
- DNA comet assay to measure 5-Fu-induced DNA damage.
Main Results:
- B7-H3 overexpression elevated BRCC3 mRNA and protein levels; B7-H3 knockdown decreased BRCC3 expression.
- An inverse correlation was observed between B7-H3 expression and 5-Fu-induced DNA damage.
- Knockdown of BRCC3 in B7-H3 overexpressing cells increased 5-Fu-induced DNA damage.
Conclusions:
- B7-H3 upregulates BRCC3 expression in colorectal cancer cells.
- BRCC3 contributes to B7-H3-induced resistance to 5-fluorouracil chemotherapy.
- BRCC3 may be a therapeutic target to overcome 5-Fu resistance in colorectal cancer.
More Related Videos
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
65
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
65
02:23Abnormal Proliferation
5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
02:36DNA Damage can Stall the Cell Cycle
10.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K
02:36DNA Damage Can Stall the Cell Cycle
3.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.3K
02:56Treatment Resistant Cancers
3.9K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
02:57Targeted Cancer Therapies
9.1K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
9.1K