Exploring the expression profile of vitamin D receptor and its related long non-coding RNAs in patients with acute lymphoblastic leukemia.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Previous studies have indicated the involvement of vitamin D receptor (VDR) and related long noncoding RNAs (lncRNAs) signaling in the pathophysiology of several cancers. However, their contribution to ALL remains to be elucidated. METHODS: In this case-control study, 30 patients with newly diagnosed ALL and 30 age- and sex-matched healthy children were selected. Then, the level of 25(OH) vitamin D and the expression of VDR and four VDR-related lncRNAs were assessed. RESULTS: No significant difference in serum 25(OH) vitamin D was observed between patients with ALL (20.42±6.5 ng/mL) and healthy subjects (25.45±11 ng/mL). In addition, the expression of MALAT-1, HOTAIR, and P-21 was not statistically significant between the two groups. However, a significant reduction in VDR and H19 expression was observed in patients with ALL (p<0.05). CONCLUSIONS: 25(OH) vitamin D insufficiency was evident in both groups. VDR and H19 signaling might be contributed to the pathogenesis of ALL, which needs further investigations.

Exploring the expression profile of vitamin D receptor and its related long non-coding RNAs in patients with acute lymphoblastic leukemia

SUMMARY OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Previous studies have indicated the involvement of vitamin D receptor (VDR) and related long noncoding RNAs (lncRNAs) signaling in the pathophysiology of several cancers. However, their contribution to ALL remains to be elucidated. METHODS: In this case-control study, 30 patients with newly diagnosed ALL and 30 age- and sex-matched healthy children were selected. Then, the level of 25(OH) vitamin D and the expression of VDR and four VDR-related lncRNAs were assessed. RESULTS: No significant difference in serum 25(OH) vitamin D was observed between patients with ALL (20.42±6.5 ng/mL) and healthy subjects (25.45±11 ng/mL). In addition, the expression of MALAT-1, HOTAIR, and P-21 was not statistically significant between the two groups. However, a significant reduction in VDR and H19 expression was observed in patients with ALL (p<0.05). CONCLUSIONS: 25(OH) vitamin D insufficiency was evident in both groups. VDR and H19 signaling might be contributed to the pathogenesis of ALL, which needs further investigations.

Colorimetric nanoplatform for visual determination of cancer cells via target-catalyzed hairpin assembly actuated aggregation of gold nanoparticles.

According to aptamer-mediated hairpin DNA cascade amplifier and gold nanoparticles aggregation, an optical platform for cancer cells determination has been proposed. High-affinity chimeric aptamers were used for cancer cell detection and also as an initiator for beginning hairpin assembly to construct three-way junction (3WJ) nanostructures. These three hairpins were modified at 3' ends with biotin. In the presence of target cell, chimeric aptamer binds to its ligand on cell surface and initiates 3WJ nanostructures formation. These 3WJ nanostructures interact with streptavidin-modified gold nanoparticles (AuNPs) via non-covalent biotin-streptavidin interactions and create a crossover lattice of nanoparticles. This event leads to AuNPs aggregation and red-shifting. The results were confirmed by gel electrophoresis and UV-visible spectrophotometry. The dynamic range of this assay is 25 to 107 cells with a detection limit of 10 cells which is respectively 9 and 4 times more significant than the sensitivity of AuNP-based approaches without amplification and enzyme-mediated signal amplification. Graphical abstract.

DNAzyme-embedded hyperbranched DNA dendrimers as signal amplifiers for colorimetric determination of nucleic acids.

A DNAzyme-embedded hyperbranched DNA dendrimer is used as a colorimetric signal amplifier in an ultrasensitive detection scheme for nucleic acids. The hyperbranched DNA dendrimers were constructed by single-step autonomous self-assembly of three structure-free DNA monomers. A cascade of self-assembly reactions between the first and second strands leads to the formation of linear DNA concatemers containing overhang flank fragments. The third strand, which bears a peroxidase-mimicking DNAzyme domain, serves as a bridge to trigger self-assembly between the first and second strands across the side chain direction. This results in a chain branching growth of the DNAzyme-embedded DNA dendrimer. This signal amplifier was incorporated into the streptavidin-biotin detection system which comprises an adaptor oligonucleotide and a biotinylated capture probe. The resulting platform is capable of detecting a nucleic acid target with an LOD as low as 0.8 fM. Such sensitivity is comparable if not superior to most of the reported enzyme-free (and even enzyme-assisted) signal amplification strategies. The DNA dendrimer based method is expected to provide a universal platform for extraordinary signal enhancement in detecting other nucleic acid biomarkers by altering the respective sequences of adaptor and capture probe. Graphical abstract Schematic of an assembly of a DNAzyme-embedded hyperbranched DNA dendrimer which operates as a signal amplifier for nucleic acids detection. The nanostructure is constructed by autonomous self-assembly of three DNA monomers. Colored letters represent each domain, and complementary domains are marked by asterisk. Domain d represents the DNAzyme sequence.

Target-triggered three-way junction in conjugation with catalytic concatemers-functionalized nanocomposites provides a highly sensitive colorimetric method for miR-21 detection.

With the great advances in DNA nanotechnology, scientists have shown interest in developing dynamic nanostructures for theranostic applications, analyte sensing and cargo delivery. Here, we present a specific enzyme-free ultrasensitive platform based on a multilayer coupled signal amplification strategy to quantify miR-21 molecule. The biosensor was integrated based on three signal amplification gadgets, namely a translator-mediated catalytic hairpin assembly (CHA), a multilayer DNA concatemer on the surface of gold decorated magnetic nanoparticle (GMNP), and a DNAzyme-mediated catalytic signal amplification. MiR-21 mediates the release of a DNA translator from an immobilized duplex to engage in a CHA reaction using three hairpins, including a GMNP-conjugated hairpin 1 (H1), biotin-labeled hairpin 2 (H2) and a GMNP-conjugated hairpin 3 (H3) to form a three-way junction (3WJ). Meanwhile, a plenty of initiator strand 0 (S0) on GMNPs - each of which has been bifunctionalized with S0/H1 or S0/H3 - drive several multilayer peroxidase-mimicking DNAzyme concatemers in the presence of two accessory oligonucleotides; strand 1 (S1) and strand 2 (S2). Since a G-rich sequence was attached at the 5'-end of S1 strand, in the presence of hemin cofactor, an active G-quadruplex DNAzyme with peroxidase activity was formed. The concatemers on the surface of GMNPs can convert a colorless substrate to a green product. The biosensor can detect as low as 1 aM of miR-21 and provide an excellent capability to discriminate single-base mismatches. The required time for the formulation of the assay reagents is about three days and the reaction time for the detection of miR-21 takes place in less than four hours.

Aptamer-integrated DNA nanoassembly: A simple and sensitive DNA framework to detect cancer cells.

The development of powerful techniques to detect cancer cells at early stages plays a notable role in diagnosing and prognosing cancer patients and reducing mortality. This paper reports on a novel functional DNA nanoassembly capable of detecting cancer cells based on structural DNA nanotechnology. DNA nanoassemblies were constructed by the self-assembly of a DNA concatemer to a plenty of sticky-ended three-way junctions. While an aptamer moiety guided the nanoassembly to the target cancer cell, the peroxidase-mimicking DNAzymes embedded in the nanoassemblies were used as the sensing element to produce colorimetric signals. As proof-of-concept, as low as 175 cancer cells were detected by the assay, and color change was clearly distinguished by the naked eyes. The proposed system enjoys potential applications for point-of-care cancer diagnosis, with its excellent sensitivity and selectivity.