Publications by authors named "Shiqi Deng"

9 Publications

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MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.

Heliyon 2021 Apr 12;7(4):e06695. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.

Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065298PMC
April 2021

Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.

Aging (Albany NY) 2021 Apr 12;13(7):10749-10769. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen 518060, Guangdong, P.R. China.

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration . We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic β-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions , suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.
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http://dx.doi.org/10.18632/aging.202895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064165PMC
April 2021

Non-intubated video-assisted thoracic surgery for subxiphoid anterior mediastinal tumor resection.

Ann Transl Med 2021 Mar;9(5):403

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.

Background: Subxiphoid approach for mediastinal tumor resection was reported to provide a better view and less postoperative pain. Non-intubated video-assisted thoracic surgery (NI-VATS) without muscle relaxant would decrease the possibility of postoperative airway collapse for anterior mediastinal mass operation. Herein, we sought to describe the use of NI-VATS through subxiphoid approach for anterior mediastinal tumor resection.

Methods: In this retrospective cohort study, patients that underwent subxiphoid VATS resection for anterior mediastinal tumor between December 2015 and September 2019 were divided into two groups: NI-VATS and intubated VATS (I-VATS). Intraoperative and postoperative variables were compared.

Results: A total of 40 patients were included. Among them, 21 patients received NI-VATS (52.5%) and 19 were treated with I-VATS (47.5%). In total, intraoperative (4/21 . 2/19; P=0.446) and postoperative complications (5/21 . 7/19; P=0.369) were similar between NI-VATS and I-VATS group. The anesthesia time (231.76 . 244.71 min; P=0.218), the operation time (152.35 . 143.64 min; P=0.980), chest tube duration (1.81 . 1.84 days; P=0.08), the total volume (351.95 . 348.00 mL; P=0.223), post-operative pain scores (2.79 . 2.93, P=0.413), and the length of stay (9.47 . 10.57 days; P=0.970) were all comparable between two groups.

Conclusions: NI-VATS for mediastinal tumor resection via subxiphoid approach is a safe and technically feasible option in selected patients, which leads to comparable perioperative clinical outcomes when compared with I-VATS via the subxiphoid approach. This technique could be used as an alteration when intubation is not available.
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http://dx.doi.org/10.21037/atm-20-6125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033331PMC
March 2021

SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.

Cell Cycle 2020 10 5;19(20):2720-2733. Epub 2020 Oct 5.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine , Shenzhen, Guangdong, China.

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.
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http://dx.doi.org/10.1080/15384101.2020.1826632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644164PMC
October 2020

miRNA-192 and -215 activate Wnt/β-catenin signaling pathway in gastric cancer via APC.

J Cell Physiol 2020 09 24;235(9):6218-6229. Epub 2020 Feb 24.

Department of Pathology, Guangdong Key Laboratory for Genome Stability & Disease Prevention, The Shenzhen University School of Medicine, Shenzhen, Guangdong, China.

Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA-192 and -215. In summary, miRNA-192 and -215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.
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http://dx.doi.org/10.1002/jcp.29550DOI Listing
September 2020

Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer.

Oncol Rep 2018 Dec 8;40(6):3323-3334. Epub 2018 Oct 8.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, P.R. China.

A mounting body of evidence has revealed that microRNAs (miRs) serve pivotal roles in various developmental processes, and in tumourigenesis, by binding to target genes and subsequently regulating gene expression. Continued activation of the Wnt/β‑catenin signalling is positively associated with human malignancy. In addition, miR‑194 dysregulation has been implicated in gastric cancer (GC); however, the molecular mechanisms underlying the effects of miR‑194 on GC carcinogenesis remain to be elucidated. The present study demonstrated that miR‑194 was upregulated in GC tissues and SUFU negative regulator of Ηedgehog signaling (SUFU) was downregulated in GC cell lines. Subsequently, inhibition of miR‑194 attenuated nuclear accumulation of β‑catenin, which consequently blocked Wnt/β‑catenin signalling. In addition, the cytoplasmic translocation of β‑catenin induced by miR‑194 inhibition was mediated by SUFU. Furthermore, genes associated with the Wnt/β‑catenin signalling pathway were revealed to be downregulated following inhibition of the Wnt signalling pathway by miR‑194 suppression. Finally, the results indicated that cell apoptosis was markedly increased in response to miR‑194 inhibition, strongly suggesting the carcinogenic effects of miR‑194 in GC. Taken together, these findings demonstrated that miR‑194 may promote gastric carcinogenesis through activation of the Wnt/β‑catenin signalling pathway, making it a potential therapeutic target for GC.
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http://dx.doi.org/10.3892/or.2018.6773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196585PMC
December 2018

Inhibition of the miR-192/215-Rab11-FIP2 axis suppresses human gastric cancer progression.

Cell Death Dis 2018 07 13;9(7):778. Epub 2018 Jul 13.

Department of Pathology, School of Basic Medical Sciences, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen Key Laboratory of Micromolecule Innovatal Drugs, Shenzhen University Health Sciences Center, Shenzhen, Guangdong, People's Republic of China.

Less than a century ago, gastric cancer (GC) was the most common cancer throughout the world. Despite advances in surgical, chemotherapeutic, and radiotherapeutic treatment, GC remains the number 3 cancer killer worldwide. This fact highlights the need for better diagnostic biomarkers and more effective therapeutic targets. RAB11-FIP2, a member of the Rab11 family of interacting proteins, exhibits potential tumor suppressor function. However, involvement of RAB11-FIP2 in gastric carcinogenesis is yet to be elucidated. In this study, we demonstrated that RAB11-FIP2 was downregulated in GC tissues and constituted a target of the known onco-miRs, miR-192/215. We also showed that functionally, Rab11-FIP2 regulation by miR-192/215 is involved in GC-related biological activities. Finally, RAB11-FIP2 inhibition by miR-192/215 affected the establishment of cell polarity and tight junction formation in GC cells. In summary, this miR-192/215-Rab11-FIP2 axis appears to represent a new molecular mechanism underlying GC progression, while supplying a promising avenue of further research into diagnosis and therapy of GC.
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http://dx.doi.org/10.1038/s41419-018-0785-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045576PMC
July 2018

SMG-1 inhibition by miR-192/-215 causes epithelial-mesenchymal transition in gastric carcinogenesis via activation of Wnt signaling.

Cancer Med 2018 01 13;7(1):146-156. Epub 2017 Dec 13.

Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, China.

SMG-1,a member of the phosphoinositide kinase-like kinase family, functioned as a tumor suppressor gene. However, the role of SMG-1 in GC remain uncharacterized. In this study, regulation of SMG-1 by miR-192 and-215, along with the biological effects of this modulation, were studied in GC. We used gene microarrays to screening and luciferase reporter assays were to verify the potential targets of miR-192 and-215. Tissue microarrays analyses were applied to measure the levels of SMG-1 in GC tissues. Western blot assays were used to assess the signaling pathway of SMG-1 regulated by miR-192 and-215 in GC. SMG-1 was significantly downregulated in GC tissues.The proliferative and invasive properties of GC cells were decreased by inhibition of miR-192 and-215, whereas an SMG-1siRNA rescued the inhibitory effects. Finally, SMG-1 inhibition by miR-192 and-215 primed Wnt signaling and induced EMT. Wnt signaling pathway proteins were decreased markedly by inhibitors of miR-192 and-215, while SMG-1 siRNA reversed the inhibition apparently. Meanwhile, miR-192 and-215 inhitibtors increased E-cadherin expression and decreased N-cadherin and cotransfection of SMG-1 siRNA reversed these effects. In summary, these findings illustrate that SMG-1 is suppressed by miR-192 and-215 and functions as a tumor suppressor in GC by inactivating Wnt signaling and suppressing EMT.
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http://dx.doi.org/10.1002/cam4.1237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773975PMC
January 2018

Hydrothermal synthesis of single-crystalline perovskite PbTiO3 nanosheets with dominant (001) facets.

Inorg Chem 2014 Oct 29;53(20):10937-43. Epub 2014 Sep 29.

State Key Laboratory of Silicon Materials, Department of Materials Science and Engineering, and Key Laboratory of Advanced Materials and Applications for Battery of Zhejiang Province, Zhejiang University , Hangzhou 310027, China.

Single-crystalline tetragonal perovskite lead titanate (PbTiO3) nanosheets with dominant (001) facets have been successfully synthesized by employing layered K2Ti6O13 nanofibers as titanium sources. The as-prepared PbTiO3 nanosheets were characterized by means of X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, and selected-area electron diffraction. In order to understand the formation mechanism of the PbTiO3 nanosheets, a series of time-dependent experiments were performed. Because of the substitution of Pb(2+) ions for K(+) ions, the TiO6 octahedral lamellas exfoliate from the layered K2Ti6O13 crystal structure. Then the exfoliated TiO6 octahedral lamellas as templates transform to lamellar PbTiO3 species by reacting with the dehydrated Pb(2+) ions. With hydrothermal treatment prolongation, the lamellar PbTiO3 species crystallize to single-crystalline PbTiO3 nanosheets. Moreover, the thickness of the synthesized single-crystalline PbTiO3 nanosheets can be tailored in the range of 10-50 nm by controlling the hydrothermal treatment time. In addition, the band gap and the optoelectronic properties of the single-crystalline PbTiO3 nanosheets are investigated by UV-vis absorption and photoluminescence.
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http://dx.doi.org/10.1021/ic501180gDOI Listing
October 2014