lncRNA RMRP Prevents Mitochondrial Dysfunction and Cardiomyocyte Apoptosis via the miR-1-5p/hsp70 Axis in LPS-Induced Sepsis Mice

Han, Ying; Cai, Yong; Lai, Xiaoquan; Wang, Zhenling; Wei, Song; Tan, Kun; Xu, Min; Xie, Hongyan

doi:10.1007/s10753-019-01141-8

Cited by 57 publications

(32 citation statements)

References 41 publications

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“…Gu et al, proposed that tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG [15]. Interestingly, Han et al, inferred that inhibition of LPS-induced cardiomyocyte apoptosis and mitochondrial damage by suppressing post-transcriptional regulation of HSPA4 by miR-1-5p [16]. Although many HSPA4 have been reported to be involved in tumor biological processes, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.

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Section: Introductionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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“…In this study, H 2 O 2 treatment attenuated ΔΨm and enhanced Bax expression in NRVMs, and these effects were reversed by pretreatment with IκBα or PDTC. NF-κB is involved in the regulation of mitochondrial dysfunction [31], and Bax antagonizes the anti-apoptotic ability of Bcl-2 and simultaneously promotes permeability of the mitochondrial outer membrane and reduces the level of ΔΨm [32]. The results herein suggest that IκBα decreases cell injury and apoptosis by inhibiting NF-κB activation and Bax expression, ultimately elevating ΔΨm after H 2 O 2 stimulation.…”

Section: Discussionmentioning

confidence: 63%

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation

et al. 2020

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Background: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H 2 O 2) by inhibiting the NF-κB pathway. Methods: The IκBα S32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H 2 O 2 treatment. NRVMs were divided into control, H 2 O 2 , GFP + H 2 O 2 , IκBα+H 2 O 2 , and pyrrolidine dithiocarbamate (PDTC) + H 2 O 2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H 2 O 2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis-and autophagy-related proteins. Results: IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H 2 O 2. Meanwhile, IκBα overexpression decreased H 2 O 2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H 2 O 2 stimulation.

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“…In another work the interaction between the lncRNA component of mitochondrial RNA processing (RMRP) and miR-1-5p was evaluated [77]. Herein, the protective role of RMRP against myocardial sepsis-induced injury and mitochondrial damage was reported.…”

Section: Mirna Expression In Sepsis-related Cardiac Dysfunctionmentioning

confidence: 99%

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review

Manetti

Maiese

Paolo

et al. 2020

IJMS

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Sepsis is a severe condition characterized by systemic inflammation. One of the most involved organs in sepsis is the heart. On the other hand, heart failure and dysfunction are some of the most leading causes of death in septic patients. miRNAs are short single-strand non-coding ribonucleic acids involved in the regulation of gene expression on a post-transcriptional phase, which means they are a part of the epigenetic process. Recently, researchers have found that miRNA expression in tissues and blood differs depending on different conditions. Because of this property, their use as serum sepsis biomarkers has also been explored. A narrative review is carried out to gather and summarize what is known about miRNAs’ influence on cardiac dysfunction during sepsis. When reviewing the literature, we found at least 77 miRNAs involved in cardiac inflammation and dysfunction during sepsis. In the future, miRNAs may be used as early sepsis-induced cardiac dysfunction biomarkers or as new drug targets. This could help clinicians to early detect, prevent, and treat cardiac damage. The potential role of miRNAs as new diagnostic tools and therapeutic strategies worth deepening the complex network between non-coding RNA and biological pathways. Additional studies are needed to further investigate their role in sepsis-induced myocardium injury.

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lncRNA RMRP Prevents Mitochondrial Dysfunction and Cardiomyocyte Apoptosis via the miR-1-5p/hsp70 Axis in LPS-Induced Sepsis Mice

Cited by 57 publications

References 41 publications

HSPA4 knockdown retarded progression and development of colorectal cancer

HSPA4 knockdown retarded progression and development of colorectal cancer

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review

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