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Published on: November 30, 2016
Spatially Selective MicroRNA Imaging in Human Colorectal Cancer Tissues Using a Multivariate-Gated Signal
Xiaoming Zhang1, Wenhui Chen1, Songlin Wan1
1College of Chemistry and Molecular Sciences, Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Institute of Molecular Medicine, Renmin Hospital of Wuhan University, School of Microelectronics, Wuhan University, Wuhan 430072, P. R. China.
Abstract:
MicroRNA (miRNA) is involved in the genesis in viand development of colorectal cancer. The in vivo imaging of miRNA at the tumor sites is essential for understanding its role in colorectal cancer pathology and therapeutic target identification. However, achieving accurate imaging of miRNA at the tumor sites is hindered by the low abundance of miRNAs in tumor cells and nonspecific signal leakage in normal tissues. Here, we report a multivariate-gated catalytic hairpin assembly (CHA) nanosensor for the specific amplified imaging of microRNA-21 (miR-21) in human colorectal cancer tissues to reveal the underlying miR-21-associated molecular mechanism. The endogenous glutathione and exogenous near-infrared multivariate-gated design in combination with CHA probes improves the signal strength of target miR-21 and reduces the background interference. The nanosensor enables specific amplified imaging of miR-21 in vivo, and the signal-to-background ratios are 1.6-fold compared with traditional CHA methods. With the assistance of the designed nanosensor, we achieve the preliminary identification of tumor tissues and normal tissues from human clinical surgical resection samples. The overexpressed miR-21 is found to suppress the core mismatch repair recognition protein human mutS homologue 2 involved in DNA damage recognition and repair to inhibit the therapeutic efficacy of colorectal cancer. The strategy of probe design, which combines multivariate-gated activation methods with a signal amplification system, is applicable for accurate miRNA imaging and disease-relevant molecular mechanism research.
Insights
A novel nanosensor enables precise in vivo imaging of microRNA-21 (miR-21) in colorectal cancer, revealing its role in suppressing DNA repair and impacting treatment efficacy.
Area of Science:
- Biomedical Engineering
- Molecular Oncology
- Diagnostic Imaging
Background:
- MicroRNA (miRNA) dysregulation is crucial in colorectal cancer (CRC) development and progression.
- Accurate in vivo imaging of miRNAs in tumors is vital for understanding CRC pathology and identifying therapeutic targets.
- Challenges include low miRNA abundance and background signal in normal tissues, hindering precise imaging.
Purpose of the Study:
- To develop a specific, amplified imaging nanosensor for microRNA-21 (miR-21) in human colorectal cancer tissues.
- To elucidate the molecular mechanism underlying miR-21's role in CRC.
- To improve the accuracy of in vivo miRNA detection for clinical applications.
Main Methods:
- A multivariate-gated catalytic hairpin assembly (CHA) nanosensor was designed, incorporating endogenous glutathione and exogenous near-infrared triggers.
- The nanosensor utilizes CHA probes for signal amplification and background noise reduction.
- In vivo imaging and analysis of miR-21 expression in human colorectal cancer and normal tissues were performed.
Main Results:
- The nanosensor achieved specific amplified imaging of miR-21 in vivo with a 1.6-fold improvement in signal-to-background ratio compared to traditional CHA methods.
- Preliminary identification of tumor and normal tissues from clinical samples was achieved.
- Overexpressed miR-21 was found to suppress human mutS homologue 2, a DNA repair protein, thereby inhibiting CRC therapeutic efficacy.
Conclusions:
- The developed multivariate-gated CHA nanosensor enables accurate and amplified in vivo imaging of miR-21 in colorectal cancer.
- This approach facilitates the investigation of miRNA-associated molecular mechanisms, such as miR-21's suppression of DNA repair pathways.
- The strategy holds promise for advancing miRNA imaging and molecular mechanism research in cancer.
