scholarly journals Negatively Regulated by miR-29c-3p, MTFR1 Promotes the Progression and Glycolysis in Lung Adenocarcinoma via the AMPK/mTOR Signalling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongmeng Li ◽  
Yanfei Liu ◽  
Kai Jin ◽  
Rui Dong ◽  
Cun Gao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Quantitative Polymerase Chain Reaction ◽  
Signalling Pathway ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Biological Functions ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

Background: Lung adenocarcinoma (LUAD) is the major form of lung cancer that presents a major peril to public health. Owing to the high rates of morbidity, mortality and chemoresistance, it is necessary to develop more effective therapeutic targets of LUAD. Mitochondrial fission regulator 1 (MTFR1) affects the occurrence and development of some diseases by regulating mitochondrial dynamics and is dysregulated in LUAD. However, the functions and molecular mechanisms of MTFR1 in LUAD have not been investigated.Methods: Immunohistochemical (IHC) analysis, real-time quantitative polymerase chain reaction (RT-qPCR), bioinformatic analysis and western blot (WB) were performed to assess the expression of MTFR1 at both protein and mRNA levels. The biological functions of MTFR1 in LUAD cells were assessed based on various in vivo and in vitro experiments. The dual-luciferase reporter assay and some rescue experiments were performed to evaluate the underlying mechanism of MTFR1 in LUAD.Results: MTFR1 was upregulated in LUAD cells and tissues and correlated with dismal clinicopathologic features and a worse prognosis of patients with LUAD. Functionally, MTFR1 overexpression stimulated the proliferation, invasion, migration and glycolytic capacity and impeded the apoptosis of LUAD cells; however, opposite results were obtained when MTFR1 expression was knocked down. MTFR1, which was directly targeted by miR-29c-3p, may exert its biological functions through the AMPK/mTOR signalling pathway.Conclusion: MTFR1 promotes the progression of LUAD. Therefore, targeting MTFR1 can offer an effective therapeutic strategy for LUAD treatment.

scholarly journals MiR-107 confers chemoresistance to colorectal cancer by targeting calcium-binding protein 39

2020 ◽  
Vol 122 (5) ◽  
pp. 705-714 ◽  
Author(s):  
Yu Liang ◽  
Danxi Zhu ◽  
Lidan Hou ◽  
Yu Wang ◽  
Xin Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Calcium Binding ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Signalling Pathway ◽  
Critical Event ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

Abstract Background Chemoresistance remains a critical event that accounts for colorectal cancer (CRC) lethality. The aim of this study is to explore the ability of dichloroacetate (DCA) to increase chemosensitivity in CRC and the molecular mechanisms involved. Methods The effects of combination treatment of DCA and oxaliplatin (L-OHP) were analysed both in vitro and in vivo. The DCA-responsive proteins in AMPK pathway were enriched using proteomic profiling technology. The effect of DCA on CAB39–AMPK signal pathway was analysed. In addition, miRNA expression profiles after DCA treatment were determined. The DCA-responsive miRNAs that target CAB39 were assayed. Alterations of CAB39 and miR-107 expression were performed both in vitro and on xenograft models to identify miR-107 that targets CAB39–AMPK–mTOR signalling pathway. Results DCA increased L-OHP chemosensitivity both in vivo and in vitro. DCA could upregulate CAB39 expression, which activates the AMPK/mTOR signalling pathway. CAB39 was confirmed to be a direct target of miR-107 regulated by DCA. Alterations of miR-107 expression were correlated with chemoresistance development in CRC both in vitro and in vivo. Conclusion These findings suggest that the miR-107 induces chemoresistance through CAB39–AMPK–mTOR pathway in CRC cells, thus providing a promising target for overcoming chemoresistance in CRC.

scholarly journals LINC00942 Promotes Tumor Proliferation and Metastasis in Lung Adenocarcinoma via FZD1 Upregulation

2021 ◽  
Vol 20 ◽  
pp. 153303382097752
Author(s):  
Ronghua Wang ◽  
Xiuyun Wang ◽  
Jingtao Zhang ◽  
Yanpei Liu
Keyword(s):  
Lung Adenocarcinoma ◽  
Wnt Signaling ◽  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Regulatory Relationship ◽  
Potential Biomarker ◽  
Proliferation And Metastasis ◽  
Tumor Proliferation And Metastasis ◽  
Dual Luciferase Reporter Assay

Background: Long non-coding RNAs (lncRNAs) have been reported to play important roles in the progression of human cancers. Herein, bioinformatic analysis identified that LINC00942 was a highly overexpressed lncRNA in lung adenocarcinoma (LUAD). The present study aimed to explore the roles and possible molecular mechanisms of LINC00942 in LUAD. Methods: First, on the basis of TCGA database, the expression and prognosis of LINC00942 were analyzed in LUAD tissues. Then, si-LINC00942 was transfected into A549 and H1299 cells to knockdown the expression of LINC00942. Cell viability was detected by MTT assay. Flow cytometry was used to analyze cell apoptosis. The expressions of PCNA, Bax, Bcl-2, and wnt/β-catenin pathway proteins were detected by western blotting. Dual-luciferase reporter assay was used to evaluate the regulatory relationship between LINC00942 and miR-5006-5p, or miR-5006-5p and FZD1. Results: We discovered that LINC00942 was up-regulated in LUAD tissues compared with adjacent tissues. Besides, we found the increased LINC00942 expression was associated with poor survival. In addition, silencing of LINC00942 suppressed the proliferation, migration, invasion and facilitated the apoptosis of A549 and H1299 cells. Moreover, silencing of LINC00942 repressed the expression of PCNA, Bcl-2, and enhanced Bax expression in A549 and H1299 cells. Mechanically, LINC00942 exerted its effects via enhancing Wnt signaling. LINC00942 functioned as competing endogenous RNA (ceRNA) by binding to miR-5006-5p, upregulating the expression of FZD1, which was a direct target of miR-5006-5p. Conclusion: Our findings indicated that LINC00942/miR-5006-5p/FZD1 axis played important roles in LUAD growth through enhancing Wnt signaling. LINC00942/miR-5006-5p/FZD1 axis might serve as a potential biomarker and therapeutic target for LUAD treatment.

scholarly journals Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Kit San Yeung ◽  
Winnie Wan Yee Tso ◽  
Janice Jing Kun Ip ◽  
Christopher Chun Yu Mak ◽  
Gordon Ka Chun Leung ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Signalling Pathway ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

scholarly journals Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

2018 ◽  
Vol 26 (9) ◽  
pp. 1317-1326 ◽  
Author(s):  
Xuyan Li ◽  
Xuanfang Zhong ◽  
Xiuhua Pan ◽  
Yan Ji
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Inverse Association ◽  
Novel Target ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

scholarly journals MicroRNA-277 targetsinsulin-like peptides 7and8to control lipid metabolism and reproduction inAedes aegyptimosquitoes

2017 ◽  
Vol 114 (38) ◽  
pp. E8017-E8024 ◽  
Author(s):  
Lin Ling ◽  
Vladimir A. Kokoza ◽  
Changyu Zhang ◽  
Emre Aksoy ◽  
Alexander S. Raikhel
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Critical Role ◽  
Target Prediction ◽  
Luciferase Reporter ◽  
Ovary Development ◽  
Mrna Levels ◽  
Essential Components ◽  
Energy Store

Hematophagous female mosquitoes transmit numerous devastating human diseases, including malaria, dengue fever, Zika virus, and others. Because of their obligatory requirement of a vertebrate blood meal for reproduction, these mosquitoes need a lot of energy; therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. Lipids are the major energy store providing the fuel required for host seeking and reproduction. They are essential components of the fat body, a metabolic tissue that is the insect analog of vertebrate liver and adipose tissue. In this study, we found that microRNA-277 (miR-277) plays an important role in regulating mosquito lipid metabolism. The genetic disruption of miR-277 using the CRISPR-Cas9 system led to failures in both lipid storage and ovary development. miR-277 mimic injection partially rescued these phenotypic manifestations. Examination of subcellular localization of FOXO protein via CRISPR-assisted, single-stranded oligodeoxynucleotide-mediated homology-directed repair revealed that insulin signaling is up-regulated in response to miR-277 depletion. In silico target prediction identified that insulin-like peptides 7 and 8 (ilp7andilp8) are putative targets of miR-277; RNA immunoprecipitation and a luciferase reporter assay confirmed thatilp7andilp8are direct targets of this miRNA. CRISPR-Cas9 depletion ofilp7andilp8led to metabolic and reproductive defects. These depletions identified differential actions of ILP7 and ILP8 in lipid homeostasis and ovarian development. Thus, miR-277 plays a critical role in mosquito lipid metabolism and reproduction by targetingilp7andilp8, and serves as a monitor to control ILP7 and ILP8 mRNA levels.

scholarly journals Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

2020 ◽  
Author(s):  
Aaron J Salisbury ◽  
Christopher A Blackwood ◽  
Jean Lud Cadet
Keyword(s):  
Glutamate Receptors ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Opioid Use Disorder ◽  
Mrna Levels ◽  
Opioid Use ◽  
Self Administration ◽  
Lever Pressing ◽  
Polymerase Chain ◽  
Long Access

People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

scholarly journals Hnf1α is required for proper gut epithelial endocrine cell specification and controls the mTOR signalling pathway in mice

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Francois Boudreau ◽  
Carine R Lussier ◽  
Francois Brial ◽  
Nathalie Rivard ◽  
Nathalie Perreault
Keyword(s):  
Endocrine Cell ◽  
Signalling Pathway ◽  
Cell Specification ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

scholarly journals miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury

2021 ◽  
pp. 1-11
Author(s):  
Yue Zhao ◽  
Yue Lang ◽  
Mingchao Zhang ◽  
Shaoshan Liang ◽  
Xiaodong Zhu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Kidney Injury ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Mitochondrial Fragmentation ◽  
Tubular Cells ◽  
Renal Tubular Cells

<b><i>Background:</i></b> Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. <b><i>Objectives:</i></b> To explore the molecular mechanisms of mitochondrial disorders and kidney damage. <b><i>Methods:</i></b> We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting ­assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. <b><i>Results:</i></b> miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.

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