Long non-coding RNA MEG3 serves as a ceRNA for microRNA-145 to induce apoptosis of AC16 cardiomyocytes under high glucose condition

AbstractDiabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes, but its pathogenesis remains largely unclear. In the present study, we aimed to explore the potential role of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) and to investigate the underlying mechanisms in human AC16 cardiomyocytes under high glucose (HG) condition. The results demonstrated that MEG3 was overexpressed in HG-treated AC16 cells, and MEG3 knockdown suppressed the HG-induced apoptosis in AC16 cells. Mechanistically, MEG3 directly binds to miR-145 in AC16 cells, thereby up-regulating the expression of PDCD4. Rescue experiments showed that the role of MEG3 in HG-treated AC16 cells was partly dependent on its suppression on miR-145. In summary, our findings suggested that the role of MEG3 in HG-treated human cardiomyocytes is to serve as a competing endogenous RNA (ceRNA), which negatively regulates miR-145. These findings may provide a valuable and promising therapeutic target for the treatment of DCM in the future.

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Role of Autophagy in Angiogenesis Induced by a High-Glucose Condition in RF/6A Cells

Ophthalmologica ◽

10.1159/000455270 ◽

2017 ◽

Vol 237 (2) ◽

pp. 85-95 ◽

Cited By ~ 10

Author(s):

Jun-Hui Du ◽

Xia Li ◽

Rong Li ◽

Bai-Xiang Cheng ◽

Manzila Kuerbanjiang ◽

...

Keyword(s):

High Glucose ◽

High Glucose Condition ◽

Glucose Condition

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Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Scientific Reports ◽

10.1038/s41598-020-72943-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Isaivani Jayachandran ◽

Saravanakumar Sundararajan ◽

Saravanakumar Venkatesan ◽

Sairaj Paadukaana ◽

Muthuswamy Balasubramanyam ◽

...

Keyword(s):

Signaling Pathway ◽

Kidney Cell ◽

High Glucose ◽

Renal Cell ◽

Asymmetric Dimethylarginine ◽

Cell Injury ◽

High Glucose Condition ◽

Erk Activity ◽

Glucose Condition

Abstract We previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.

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Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

Journal of Personalized Medicine ◽

10.3390/jpm11060513 ◽

2021 ◽

Vol 11 (6) ◽

pp. 513

Author(s):

Zheng Zhang ◽

Meng Gu ◽

Zhongze Gu ◽

Yan-Ru Lou

Keyword(s):

Molecular Mechanisms ◽

Neurological Diseases ◽

Cellular Processes ◽

Dna And Rna ◽

Chemotherapeutic Response ◽

Non Coding Rna ◽

Response To Chemotherapy ◽

Personalized Oncology ◽

Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

Open Life Sciences ◽

10.1515/biol-2021-0002 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1-13

Author(s):

Weiwei Liu ◽

Dongmei Yao ◽

Bo Huang

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Nude Mouse Model ◽

Western Blot Assay ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

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Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis

Cell Death and Disease ◽

10.1038/s41419-020-03346-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Min Lu ◽

Xinglei Qin ◽

Yajun Zhou ◽

Gang Li ◽

Zhaoyang Liu ◽

...

Keyword(s):

Acquired Resistance ◽

Transcriptional Regulators ◽

First Line ◽

Protein Coding ◽

Gemcitabine Resistance ◽

Non Coding Rna ◽

Sphere Formation ◽

Long Non Coding Rna ◽

Line Chemotherapy

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

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Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab007 ◽

2021 ◽

Author(s):

Fengyun Zhou ◽

Ting Feng ◽

Xiangqi Lu ◽

Huicheng Wang ◽

Yangping Chen ◽

...

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Role ◽

Cytochrome C Release ◽

Neonatal Cardiomyocytes ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion ◽

Underlying Mechanisms ◽

Induced Apoptosis

Abstract Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

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Retraction: Long non-coding RNA TUG1 alleviates high glucose induced podocyte inflammation, fibrosis and apoptosis in diabetic nephropathy via targeting the miR-27a-3p/E2F3 axis

RSC Advances ◽

10.1039/d1ra90045e ◽

2021 ◽

Vol 11 (9) ◽

pp. 5244-5244

Author(s):

Laura Fisher

Keyword(s):

Diabetic Nephropathy ◽

High Glucose ◽

Non Coding Rna ◽

Long Non Coding Rna

Retraction of ‘Long non-coding RNA TUG1 alleviates high glucose induced podocyte inflammation, fibrosis and apoptosis in diabetic nephropathy via targeting the miR-27a-3p/E2F3 axis’ by Yang Li et al., RSC Adv., 2019, 9, 37620–37629, DOI: 10.1039/C9RA06136C.

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