Aptamer-Based Detection of Circulating Targets for Precision Medicine

Wu, Lingling; Wang, Yidi; Xu, Xing; Liu, Yilong; Lin, Bingqian; Zhang, Mingxia; Zhang, Jialü; Wan, Shuang; Yang, Chaoyong; Tan, Weihong

doi:10.1021/acs.chemrev.0c01140

Cited by 416 publications

(258 citation statements)

References 603 publications

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“…Among them, the stability of DNA aptamers was much higher than that of RNA due to its chemical property. However, to overcome this dilemma, a wealth of synthetic chemical method has been introduced into the SELEX and post-SELEX modification process to improve the stability of aptamers [ 15 ]. For example, 2′-fluoro-, 2′-amino-, and 2′-O-methyl-substituted libraries modification make the aptamers more stable in biological application.…”

Section: Discussionmentioning

confidence: 99%

Aptamer-based cell-free detection system to detect target protein

Chen

Zhuang

Zheng

et al. 2021

Synthetic and Systems Biotechnology

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Biomarkers of disease, especially protein, show great potential for diagnosis and prognosis. For detecting a certain protein, a binding assay implementing antibodies is commonly performed. However, antibodies are not thermally stable and may cause false-positive when the sample composition is complicated. In recent years, a functional nucleic acid named aptamer has been used in many biochemical analysis cases, which is commonly selected from random sequence libraries by using the systematic evolution of ligands by exponential enrichment (SELEX) techniques. Compared to antibodies, the aptamer is more thermal stable, easier to be modified, conjugated, and amplified. Herein, an A ptamer- B ased C ell-free D etection (ABCD) system was proposed to detect target protein, using epithelial cell adhesion molecule (EpCAM) as an example. We combined the robustness of aptamer in binding specificity with the signal amplification ability of CRISPR-Cas12a′s trans -cleavage activity in the ABCD system. We also demonstrated that the ABCD system could work well to detect target protein in a relatively low limit of detection (50–100 nM), which lay a foundation for the development of portable detection devices. This work highlights the superiority of the ABCD system in detecting target protein with low abundance and offers new enlightenment for future design and development.

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Section: Discussionmentioning

confidence: 99%

Aptamer-based cell-free detection system to detect target protein

Chen

Zhuang

Zheng

et al. 2021

Synthetic and Systems Biotechnology

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“…The preliminary studies of our group showed that circulating miRNAs could be applied in the screening of BC patients, as we identi ed four plasma miRNAs and four serum miRNAs from the miR-106a-363 cluster, which could be used as new noninvasive biomarkers for BC detection [11]. Continuous liquid biopsies can indicate the dynamic evolution of tumor, re ect heterogeneity, assess the variance of different metastatic lesions, observe the effect of treatment on tumor cells and monitor clonal evolution, which would promote understanding the mechanisms of chemoresistance and provide precise and individualized treatment plans in refractory tumors [12][13][14][15][16][17]. We have explored the use of circulating miRNAs as prognostic markers for NCT, and identi ed miR-1275 was signi cantly associated to the response to NCT as well as the correlation to OS in LABC patients.…”

Section: Discussionmentioning

confidence: 99%

miR-1275 Targets MDK/AKT Signaling to Inhibit Breast Cancer Chemoresistance by Lessening the Properties of Cancer Stem Cells

Han

Wang

et al. 2021

Preprint

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Background: Chemoresistance is a major obstacle in the neoadjuvant chemotherapy (NCT) of locally advanced breast cancer (LABC). Identification of miRNAs as prognostic biomarkers may help overcome chemoresistance of breast cancer (BC). The aim of this study was to evaluate the expression level of miR-1275 in plasma samples and the biological functions in the chemoresistance of BC.Methods: The expression levels of miR-1275 in plasma samples and cells were measured by RT-qPCR. The associations between the expression levels of miR-1275 and clinicopathological features were studied. CRISPR/Cas9-mediated gene editing was used to construct miR-1275 knock-out cells. CCK-8, colony formation assays, epirubicin accumulation assay and xenograft tumor models were used to detect the sensitivity of breast cancer cells to epirubicin in vitro and in vivo. Mammosphere formation assay, flow cytometry analysis and western blot analyses were used to evaluate the effects of miR-1275 on cancer stem cells (CSCs) characteristics in BC cells. Dual-luciferase reporter, RNA pulldown, ELISA and IHC were used to verify the relationship between the expression of miR-1275 and Midkine (MDK). Results: We found that miR-1275 was significantly downregulated in plasma from patients resistant to chemotherapy with LABC and in chemoresistant breast cancer cell lines, while patients with low levels of miR-1275 show poor overall survival. Mir-1275 knock-out promoted chemoresistance in breast cancer cells by increasing the properties of cancer stem cells in vitro and in vivo. Mechanistically, we identified that Midkine was determined to be direct downstream protein of miR-1275 which initiated PI3K/Akt signaling in breast cancer cells.Conclusions: We demonstrated that the high expression level of miR-1275 in plasma predicted better response to NCT. The reduction of miR-1275 promoted BC cells chemoresistance by increasing CSC properties via targeting MDK/AKT axis. The potential of miR-1275 as a new prognostic biomarker and therapeutic target of breast cancer patients was identified.

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“…Abnormal expression of C-miRNA can distinguish healthy patients from disease patients. In addition, C-miRNA helps to identify tumor origin and classify tumor types and subtypes, which are important for cancer diagnosis, treatment and prognosis Similarly, the detection of C-miRNA still has some problems, such as expensive equipment and complex operation, which still needs further exploration [ 14 ].…”

Section: Detection Of Exosome Mirnamentioning

confidence: 99%

The role of Exosomal miRNAs in cancer

Zhou

Chen

et al. 2022

J Transl Med

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Exosomal miRNAs have attracted much attention due to their critical role in regulating genes and the altered expression of miRNAs in virtually all cancers affecting humans (Sun et al. in Mol Cancer 17(1):14, 2018). Exosomal miRNAs modulate processes that interfere with cancer immunity and microenvironment, and are significantly involved in tumor growth, invasion, metastasis, angiogenesis and drug resistance. Fully investigating the detailed mechanism of miRNAs in the occurrence and development of various cancers could help not only in the treatment of cancers but also in the prevention of malignant diseases. The current review highlighted recently published advances regarding cancer-derived exosomes, e.g., sorting and delivery mechanisms for RNAs. Exosomal miRNAs that modulate cancer cell-to-cell communication, impacting tumor growth, angiogenesis, metastasis and multiple biological features, were discussed. Finally, the potential role of exosomal miRNAs as diagnostic and prognostic molecular markers was summarized, as well as their usefulness in detecting cancer resistance to therapeutic agents.

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Aptamer-Based Detection of Circulating Targets for Precision Medicine

Cited by 416 publications

References 603 publications

Aptamer-based cell-free detection system to detect target protein

Aptamer-based cell-free detection system to detect target protein

miR-1275 Targets MDK/AKT Signaling to Inhibit Breast Cancer Chemoresistance by Lessening the Properties of Cancer Stem Cells

The role of Exosomal miRNAs in cancer

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