LncRNA RHPN1-AS1 promotes cholangiocarcinoma progression and predicts poor clinical outcome through miR-345-5p/YAP1 axis

Ma, Lifeng; Li, Tao; Liu, Guochao; Wang, Jianlong; Yin, Zhaoqiang; Kang, Jiansheng

doi:10.21203/rs.3.rs-58822/v1

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…These data revealed that DANCR downregulation could efficiently reduce the inflammatory response and oxidative stress during AS progression, contributing to our understanding of the pathogenic mechanism during AS development. In addition, DANCR has been identified as the ceRNA of several target miRNAs other than miR-214-5p, such as miR-185-5p [32], miR-874-3p [33], miR-1301-3p [34], miR-185-5p [35], miR-345-5p [36], miR-125b-5p [37], and miR-144-3p [38]. Since one lncRNA might target one or more downstream miRNAs [39], we hypothesized that DANCR might also have other target miRNAs that participated in the function of this lncRNA in AS progression.…”

Section: Discussionmentioning

confidence: 99%

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway

2022

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Background Although long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) has been reported to be involved in atherosclerosis (AS) development, its specific mechanism remains unclear. Methods DANCR expression levels in blood samples of AS patients and oxidized low-density lipoprotein (ox-LDL) treated vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The small interfering RNA targeting DANCR (si-DANCR) was used to silence DANCR expression. Cell viability was assessed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Levels of inflammatory cytokines, anti-oxidative enzyme superoxide dismutase (SOD) activity, and malonaldehyde (MDA) were detected by specific commercial kits. An animal AS model was established to confirm the role of DANCR/microR-214-5p/COX20 (the chaperone of cytochrome c oxidase subunit II COX2) in AS development. Results DANCR was significantly increased in the blood samples of AS patients and ox-LDL treated VSMCs and HUVECs. DANCR downregulation obviously increased viability and reduced apoptosis of ox-LDL-treated VSMCs and HUVECs. Meanwhile, DANCR downregulation reduced the levels of inflammatory cytokines, including interleukin (IL)-6 (IL-6), IL-1beta (IL-1β), IL-6 and tumor necrosis factor (TNF)-alpha (TNF-α) and MDA while increasing the SOD level in ox-LDL-treated VSMCs and HUVECs. DANCR regulated COX20 expression by acting as a competing endogenous RNA (ceRNA) of miR-214-5p. Rescue experiments demonstrated that miR-214-5p downregulation obviously attenuated si-DANCR-induced protective effects on ox-LDL-caused endothelial injury. Conclusions Our results revealed that DANCR promoted AS progression by targeting the miR-214-5p/COX20 axis, suggesting that DANCR might be a potential therapeutic target for AS.

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Section: Discussionmentioning

confidence: 99%

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway

2022

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“…For example, RHPN1‐AS1 increased the expression of leucine zipper/EF hand transmembrane‐containing‐1 (LETM1) in ovarian cancer via inhibiting miR‐596 expression to activate the FAK/PI3K/AKT signaling pathway to promote tumorigenesis and metastasis 11 . Other studies also demonstrated the oncogenic role of RHPN1‐AS1 in cholangiocarcinoma, 12 cervical cancer, 13 colorectal cancer, 14 gastric cancer, 15 and hepatocellular carcinoma 16 . Nevertheless, the molecular mechanism of RHPN1‐AS1 regulation in PCa tumor progression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

LncRNA RHPN1‐AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR‐7‐5p/EGFR/PI3K/AKT/mTOR signaling pathway

Ren

Zhang

et al. 2022

Environmental Toxicology

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lncRNA RHPN1-AS1 (RHPN1-AS1) has been con rmed to promote tumor progression in multiple cancers and is upregulated in prostate cancer (PCa), but whether it has an effect on PCa progression remains unclear. In this study, we found that PCa patients with high RHPN1-AS1 expression had a shorter survival time, and RHPN1-AS1 was signi cantly upregulated in PCa tissues and cells. Based on informatics analysis we predicted that miR-7-5p binds to 3'UTR of RHPN1-AS1 and epidermal growth factor receptor (EGFR) and veri ed it by luciferase reporter gene assay. Subsequently, we transfected PCa cells with RHPN1-AS1 overexpression vector (RHPN1-AS1), knockdown plasmids (sh-RHPN1-AS1) and/or miR-7-5p mimics or inhibitor and/or overexpression vector (EGFR) or small interfering RNA of EGFR (si-EGFR) or its control, and found that overexpression of RHPN1-AS1 inhibited miR-7-5p expression and promoted EGFR expression, silencing RHPN1-AS1 inhibited proliferation and invasion and induced G2/M arrest, apoptosis and autophagy in PCa cells. 3MA (an inhibitor of autophagy)-mediated autophagy inhibition attenuated RHPN1-AS1 inhibition-induced apoptosis. Overexpression miR-7-5p or silencing EGFR promoted LC3-I to LC3-II conversion, enhanced autophagy activity, induced cleaved-caspase-3 expression and apoptosis in PCa cells. Furthermore, we found that overexpression of RHPN1-AS1 promoted phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR, inhibited LC3-I to LC3-II conversion and reduced apoptosis in PCa cells, while GSK2126458 (an inhibitor of PI3K) reversed the effect of RHPN1-AS1 on PCa cells. In summary, RHPN1-AS1 acted as a ceRNA of miR-7-5p to upregulate EGFR expression, silencing RHPN1-AS1 suppressed PCa tumor progression by inducing autophagy and apoptosis in PCa cells through the miR-7-5p/EGFR/PI3K/AKT/mTOR pathway.

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The effect of genetics and biochemistry on the pathogenesis of cholangiocarcinoma

Ucdal,

Burus,

Celtikci

2024

Int J Hepatobiliary Pancreat Dis

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Cholangiocarcinoma (CCA) presents a significant therapeutic challenge due to its poor prognosis and the complex interplay of metabolic pathways in its development. This study aims to elucidate the genetic, biochemical, and metabolic factors contributing to CCA’s pathogenesis to inform more targeted and effective treatment strategies. A comprehensive review of the current literature was conducted, focusing on the role of genetic variations and metabolic disruptions in CCA. Key pathways such as PI3K/AKT/mTOR, FGFR, and IDH were examined, along with their impacts on carbohydrate, lipid, nucleic acid, and amino acid metabolism. The findings indicate that the liver’s vital role in regulating these metabolic processes means that disruptions can profoundly influence disease progression. Genetic variations were found to significantly alter both metabolic and signaling pathways, contributing to the aggressive nature of CCA. Understanding the complexities of genetic and metabolic interplay in CCA is essential for developing more targeted and effective treatment strategies. This review highlights the importance of these pathways in the pathogenesis of CCA and suggests potential therapeutic targets for future research.

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LncRNA RHPN1-AS1 promotes cholangiocarcinoma progression and predicts poor clinical outcome through miR-345-5p/YAP1 axis

Cited by 3 publications

References 20 publications

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway

LncRNA RHPN1‐AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR‐7‐5p/EGFR/PI3K/AKT/mTOR signaling pathway

The effect of genetics and biochemistry on the pathogenesis of cholangiocarcinoma

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