INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2018
·Vol. 19
·期 2
·447
·
IF 3.687
Ze-Qun Jiang,Mu-Han Li,Yue-Mu Qin,Hai-Ying Jiang,Xu Zhang,Mian-Hua Wu
Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.Keywords:luteolin;apoptosis;non-small cell lung cancer;microRNA-34a-5p
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 28
·1801118
·
IF 13.325
Hai-Jun Liu,Xin Luan,Hai-Yi Feng,Xiao Dong,Si-Cong Yang,Zhong-Jian Chen,Qin-Yi Cai,Qin Lu,Yunpeng Zhang,Peng Sun,Mei Zhao,Hong-Zhuan Chen,Jonathan F. Lovell,Chao Fang
Mesoporous silica nanoparticles (MSN) can load and deliver potentially synergistic anticancer agents such as small molecule cytotoxics (like doxorubicin, DOX) and nucleic acids (like microRNA, miRNA). However, these cargos have different underlying chemical properties so overcoming respective intracellular delivery barriers is a key consideration. Strategies to deliver DOX from MSN frequently employ pH-driven mechanisms that are restricted to the acidic environment of lysosomes. Conversely, strategies to deliver miRNA make use of approaches that deliberately compromise lysosomal membrane integrity to enable cytosolic delivery of the payload. To reconcile these two needs (lysosomal delivery of DOX and intracellular delivery of miRNA), a new methodology by “weaving” polyethylenimine on the MSN surface through disulfide bonds to achieve superior delivery of chemotherapy (DOX) and miRNA therapy (using miRNA-145) is developed. Furthermore, an active targeting strategy based on a peptide ligand with affinity to glucose-regulated protein 78 (GRP78), a cell surface protein overexpressed in colorectal carcinoma, is developed. The active targeting approach results in enhanced synergistic antitumor effect both in vitro and in vivo in an orthotopic murine model of colorectal cancer. Taken together, this work demonstrates the capability and advantages of “smart” MSN delivery systems to deliver anticancer cargo appropriately to targeted cancer cells.
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Bioengineered
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2021
·
IF 3.269
Shanzhi Wan,Zhimin Liu,Yang Chen,Zhitao Mai,Mingming Jiang,Qingguo Di,Baohua Sun
MicroRNA (miR)-140-3p has been proved to repress lung adenocarcinoma (LUAD), and our study aims to further evaluate the mechanism. Bioinformatic analyses were performed. The viability, proliferation, migration, invasion and angiogenesis of transfected LUAD cells were all determined via Cell Counting Kit-8, colony formation, Scratch, Transwell, and tube formation assays. The targeting relationship between miR-140-3p and thymidylate synthetase (TYMS) was confirmed by dual-luciferase reporter assay. Relative expressions of miR-140-3p, TYMS, epithelial-to-mesenchymal transition- (E-cadherin, N-cadherin, vimentin), angiogenesis- (vascular endothelial growth factor (VEGF)), and apoptosis-related factors (cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax)) were quantified by quantitative real-time polymerase chain reaction or Western blot. TYMS was high-expressed yet miR-140-3p was low-expressed in LUAD cells. Upregulation of miR-140-3p inhibited TYMS expression, viability, colony formation, migration, invasion, and tube length within LUAD cells, while downregulation of miR-140-3p did oppositely. Silenced TYMS, the downstream target gene of miR-140-3p, reversed the effects of miR-140-3p downregulation on TYMS expression, cell viability, colony formation, migration, invasion, and tube length as well as the metastasis-, apoptosis- and angiogenesis-related proteins in LUAD cells. Upregulation of miR-140-3p inhibited the proliferation, migration, invasion and angiogenesis of LUAD cells via targeting TYMS.
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Bioengineered
·
2021
·
IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
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ACS Applied Nano Materials
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2021
·
IF 5.097
Xing-Yuan Du,Shao-Hua Wu,Xiao-Bin Huang,Jian-Jun Sun
Surface-enhanced Raman scattering (SERS)-based biosensing has strong potential owing to its high sensitivity and good selectivity. In this study, a SERS biosensing platform for microRNA-21 detection was proposed by combining heating-enhanced duplex-specific nuclease (DSN)-assisted target recycling amplification and silver nanocube (AgNC)-based SERS enhancement. The activity of DSN was greatly enhanced by increasing the surface temperature of a heated Au electrode (HAuE) during the DSN-assisted target recycling process, resulting in dramatic miRNA-21 amplification detection. 4-Mercaptobenzoic acid (4-MBA) acting as a Raman reporter was immobilized onto the surface of AgNC to form a AgNC/4-MBA SERS tag with AgNC providing significantly larger electric field enhancement and thus excellent SERS applications compared with conventional silver or gold nanospheres. This enhancement was attributed to the well-known “lighting rod” effect derived from the sharp geometrical feature of the edges and corners of AgNCs. These factors lead to the high sensitivity of the proposed SERS biosensor for the miRNA-21 measurement. A limit of detection of 2.88 fM (S/N = 3) was achieved at an electrode temperature of 55 °C, which was decreased by more than three magnitudes compared with that at 25 °C.
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JOURNAL OF BIOSCIENCES
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2021
·Vol. 46
·期 1
·1-12
·
IF 1.826
Yang Mingzhu,Wang Li
Asthma has significant impacts on living quality particularly in children. Long noncoding RNA (lncRNA) MALAT1 plays a crucial role in neonatal respiratory diseases. Meanwhile, MALAT1 knockdown could induce viability and attenuate apoptosis of airway-related cells. However, the role of MALAT1 in neonatal asthma, asthma-related cell, and its possible mechanism is unclear. This study aims to investigate MALAT1 level in asthma and to identify the effects of MALAT1 on bronchial/tracheal smooth muscle cells (B/TSMCs). Newborn asthma modeling rat was constructed by introducing ovalbumin (OVA). MALAT1 levels in tissues or B/TSMCs were determined by RT-qPCR. Exogenous changes of MALAT1, RyR2 or miR-133a in B/TSMCs were fulfilled by cell transfection; cell apoptosis was measured by using Cell Death Detection ELISA kit and Hochest33342; IL-6, TNF-α and IL-1β level was detected by using corresponding ELISA kit; ryanodine receptor 2 (RyR2) mRNA and miR-133a level was determined by RT-qPCR; cleaved caspase-3 (c-caspase-3) and RyR2 expression was detected by Western blot; luciferase reporter assay was performed to confirm the target regulation of miR-133a on RyR2. We found that MALAT1 was significantly upregulated in tracheal tissues of newborn asthma modeling rats. In MALAT1-silenced or -overexpressed B/TSMCs, we found a synchronous change of cell apoptosis, inflammatory factor secretion (IL-6, TNF-α, and IL-1β) or RyR2 level, but a reverse change of miR-133a level with MALAT1. Besides, MALAT1 induced B/TSMCs apoptosis and inflammation increase could be partially reversed when RyR2 was silenced or when miR-133a was overexpressed. The luciferase reporter assay confirmed that RyR2 is a direct target gene of miR-133a in B/TSMCs. Finally, we conclude that MALAT1 knockdown could protect from B/TSMCs injury via regulating miR-133a/RyR2 axis.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2020
·Vol. 413
·期 2
·543-553
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IF 3.637
Wang Dongwei,Wang Jiasheng,Song Zhiling,Hui Ni
Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling.
Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2020
·Vol. 37
·期 2
·111-120
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IF 1.737
Shi Liu,Ying Gong,Xue-Dong Xu,Hui Shen,Shuai Gao,Hai-Dong Bao,Shi-Bin Guo,Xue-Feng Yu,Jian Gong
Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.
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Experimental and Therapeutic Medicine
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2020
·Vol. 20
·期 6
·1-1
·
IF 1.785
Tongtong Niu,Yan An,Tingting Lv,Dongning Liu
Diabetic retinopathy (DR) is a serious complication of diabetes and the most common metabolic disorder. Recently, long non‑coding (lnc)RNAs have been identified as critical regulators of DR. Ribosomal protein SA pseudogene 52 (RPSAP52) is an oncogenic lncRNA expressed in pituitary tumors. The present study aimed to investigate the functions of RPSAP52 in DR. RPSAP52 levels in the plasma of diabetic patients with or without DR complication was detected. Luciferase reporter assays, RT‑qPCR and western blotting were performed to detect the interaction between RPSAP52 and micro RNA (miR)‑365. Moreover, expression vectors of RPSAP52 and Timp3, as well as miR‑365 mimics were transfected into ARPE‑19 cells exposed to high glucose and the apoptotic cells were detected. The results showed that RPSAP52 was downregulated in patients with DR compared with patients with diabetes without obvious complications. RPSAP52 directly interacted with miR‑365, while overexpression of RPSAP52 and miR‑365 did not affect the expression of one another. In addition, overexpression of RPSAP52 upregulated TIMP metallopeptidase inhibitor 3 (Timp3) in retinal pigment epithelial (RPE) cells. High glucose treatment led to downregulated RPSAP52 and Timp3, but upregulated miR‑365 in RPE cells. Moreover, cell apoptosis analysis identified that overexpression of RPSAP52 and Timp3 led to a decreased apoptotic rate of RPE cells under high glucose treatment. Therefore, it was speculated that RPSAP52 may upregulate Timp3 by serving as the endogenous sponge of miR‑365 in DR to suppress RPE cell apoptosis.
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Small
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2020
·Vol. 16
·期 19
·2000460
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IF 11.459
Manshu Peng,Feifei Sun,Na Na,Jin Ouyang
Nanogap antennas are plasmonic nanostructures with a strong electromagnetic field generated at the gap region of two neighboring particles owing to the coupling of the collective surface plasmon resonance. They have great potential for improving the optical properties of fluorophores. Herein, nanogap antennas are constructed using an aqueous solution-based method to overcome the defects of weak fluorescence and photobleaching associated with traditional organic dyes, and a highly sensitive nanogap antenna-based sensing strategy is presented for the detection of low-abundance nucleic acid biomarkers via a target-triggered strand displacement amplification (SDA) reaction between two DNA hairpins that are tagged to the tips of gold nanorods (Au NRs). In the presence of targets, end-to-end Au NR dimers gradually form, and the fluorophores quenched by the Au NRs exhibit a dramatic fluorescence enhancement due to the plasmon-enhanced fluorescence effect of nanogap antennas. Meanwhile, the SDA reaction results in secondary amplification of fluorescence signals. Combined with single-molecule counting, this method applied in miRNA-21 detection can achieve a low detection limit of 97.2 × 10 −18 m . Moreover, accurate discrimination between different cells through miRNA-21 imaging demonstrates the potential of this method in monitoring the expression level of low-abundance nucleic acid biomarkers.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Sze Shin Low,Yixin Pan,Daizong Ji,Yaru Li,Yanli Lu,Yan He,Qingmei Chen,Qingjun Liu
Circulating microRNAs (miRNAs) are effective cancer biomarkers that are highly stable in body fluids enabling noninvasive detection. Portable, low-cost and efficient biosensing systems is crucial for early on-site diagnosis, especially in resource-limited settings. Present work deals with the development of a smartphone-based biosensing system for electrochemical detection of circulating microRNA-21 (miR-21) biomarker in saliva as a proof-of-concept. The smartphone-based biosensing system composed of a disposable screen-printed biosensor modified with reduced graphene oxide/gold (rGO/Au) composite, a circuit board for detection and a Bluetooth-enabled smartphone equipped with specially designed Android application. The hybridization between miR-21 target and ssDNA probe on the rGO/Au-modified electrode resulted in the decrease in peak current with increase in miR-21 target concentration. The smartphone-based biosensing system showed comparable performance with commercial electrochemical workstation, for miR-21 detection in the concentration range of 1 × 10 −4 M to 1 × 10 -12 M with correlation coefficient (r 2 ) of 0.99. In addition to good selectivity in discriminating mismatched and non-target sequences, the biosensing system also showed acceptable recovery rate ranging from 96.2%–107.2 % in spiked artificial saliva. The smartphone-based biosensing system is envisioned to be able to realize rapid and highly sensitive detection of circulating miRNA biomarker in body fluid for point-of-care testing in remote areas.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
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2020
·Vol. 475
·期 1
·1-13
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IF 2.795
Lin Lin,Xin Bing,Jiang Tao,Wang Xin-lu,Yang Hua,Shi Tie-mei
Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.
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