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ICA inhibited the proliferation of lung cancer cells through the miR-205-5p/PTEN axis. The expression of PTEN mRNA was detected by (A) RT-qPCR, (B) CCK-8, (C) colony formation assays and (D and E) flow cytometry were used to detect proliferation, colony formation, apoptosis and cycle distribution of transfected cells in each group. Data are shown as the mean ± SD of three experiments; * P<0.05. ICA, icariin; miR, microRNA; PTEN, Phosphatase and tensin homolog deleted on chromosome ten; RT-qPCR, reverse transcription-quantitative PCR; CCK8, Cell Counting Kit-8.
Source publication
Icariin (ICA) is one of the main bioactive monomer belonging to the flavonoid glycosides that has been widely studied in multiple diseases, including lung cancer. Although ICA has shown anticancer effects, its specific molecular mechanism of action remains to be elucidated. In the present study, the expression of microRNA (miR)‑205‑5p and Phosphata...
Contexts in source publication
Context 1
... miR-205-5p/PTEN axis. Having demonstrated that PTEN is a target gene of miR-205-5p, the present study next investigated whether ICA could regulate the expression of PTEN by inhibiting miR-205-5p. In A549 cells, ICA treatment could upregulate the level of PTEN mRNA, while overexpression of miR-205-5p or downregulation of PTEN reversed that effect (Fig. 5A). In A549 cells, ICA treatment could suppress the cell vitality and colony formation effects of miR-mimic or si-PTEN transfection ( Fig. 5B and C). Moreover, FCM results showed that ICA could promote cell apoptosis and induce cell cycle arrest, while miR-205-5p or inhibition of PTEN attenuated this effect ( Fig. 5D and ...
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... the expression of PTEN by inhibiting miR-205-5p. In A549 cells, ICA treatment could upregulate the level of PTEN mRNA, while overexpression of miR-205-5p or downregulation of PTEN reversed that effect (Fig. 5A). In A549 cells, ICA treatment could suppress the cell vitality and colony formation effects of miR-mimic or si-PTEN transfection ( Fig. 5B and C). Moreover, FCM results showed that ICA could promote cell apoptosis and induce cell cycle arrest, while miR-205-5p or inhibition of PTEN attenuated this effect ( Fig. 5D and ...
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... of PTEN reversed that effect (Fig. 5A). In A549 cells, ICA treatment could suppress the cell vitality and colony formation effects of miR-mimic or si-PTEN transfection ( Fig. 5B and C). Moreover, FCM results showed that ICA could promote cell apoptosis and induce cell cycle arrest, while miR-205-5p or inhibition of PTEN attenuated this effect ( Fig. 5D and ...
Citations
... Among the top 10 upregulated miRNAs, some have been previously reported to be associated with NSCLC or other cancers, while others have not been extensively studied. Our findings are consistent with some previous reports, such as the upregulation of hsa-miR-4488, hsa-miR-205-5p, hsa-miR-92a-1-5p, and hsa-miR-551b-3p [37,40,[56][57][58][59][60][61][62]. However, our results differ from previous studies regarding hsa-miR-3180-3p and hsa-miR-3178, which were found to be downregulated [63][64][65][66][67]. Furthermore, expression of hsa-miR-6819-3p, hsa-miR-6734-5p, hsa-miR-4492, and hsa-miR-3180 in NSCLC has not been thoroughly investigated. ...
... Zhao et al. [40] demonstrated that hsa-miR-205-5p, which was the second most upregulated miRNA in our study, was overexpressed in NSCLC tissues and cell lines and promoted lung cancer cell growth and invasion by downregulating TP53INP1, consequently modulating the levels of P21, RB1, and cyclin D1. Furthermore, Zhu et al. [57] showed that hsa-miR-205-5p increased cancer cell proliferation, migration, invasion, and cell cycle progression by activating the PTEN/PI3K/AKT signaling pathway. Hsa-miR-92a, which was the fourth most upregulated miRNA in our study, was found to be overexpressed in NSCLC tissues and cell lines, and implicated in promoting epithelialmesenchymal transition (EMT) by activating the PTEN/PI3K/AKT signaling pathway, according to a study by Liu et al. [58]. ...
Simple Summary
Non-small cell lung cancer (NSCLC) is a prevalent and lethal disease. Circulating cell-free miRNA has the potential to serve as a biomarker for early detection as it reflects cancer characteristics. Through global miRNA profiling in serum samples from NSCLC patients and non-cancerous individuals, we identified 28 upregulated miRNAs in NSCLC and explored their relevance to NSCLC-related pathways. Harnessing an advanced machine-learning algorithm, we successfully developed a robust classifier capable of distinguishing NSCLC from non-cancerous cases. Our findings suggest that serum miRNAs hold promise as a valuable tool for early NSCLC diagnosis and offer valuable insights into NSCLC biology. To solidify these promising results, further validation in diverse patient cohorts is essential.
Abstract
Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.
... Icariside (ICA), the main active ingredient of Epimedium, can produce significant therapeutic effects in animal models of AS, reducing lipid accumulation and plaque formation in blood vessels. Further studies demonstrated that ICA elevated miR-205-5p expression (Zhu and Ren, 2022), promoted endothelial cell apoptosis, and inhibited their migration; silencing miR-205-5p reversed this inhibitory effect, demonstrating miR-205-5p upregulation is a potential approach for AS treatment (Huang et al., 2023). There is evidence that miR-217 can inhibit apoptosis through the TLR4/ PI3K/Akt/NF-κB pathway in atherosclerotic endothelial cells in a rat model . ...
Cardiovascular disease (CVD) is the primary cause of death in humans. Atherosclerosis (AS) is the most common CVD and a major cause of many CVD-related fatalities. AS has numerous risk factors and complex pathogenesis, and while it has long been a research focus, most mechanisms underlying its progression remain unknown. Noncoding RNAs (ncRNAs) represent an important focus in epigenetics studies and are critical biological regulators that form a complex network of gene regulation. Abnormal ncRNA expression disrupts the normal function of tissues or cells, leading to disease development. A large body of evidence suggests that ncRNAs are involved in all stages of atherosclerosis, from initiation to progression, and that some are significantly differentially expressed during AS development, suggesting that they may be powerful markers for screening AS or potential treatment targets. Here, we review the role of ncRNAs in AS development and recent developments in the use of ncRNAs for AS-targeted therapy, providing evidence for ncRNAs as diagnostic markers and therapeutic targets.
... In addition, Zhuang et al. showed that low miR-205 expression was associated with poor prognosis in patients with pancreatic cancer [33]. Notably, this miRNA has been found to target the PI3K/AKT signaling pathway in different malignancies [38][39][40]. ...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer. The symptoms appear in advanced stages, and diagnostic and prognostic tests for the early detection of PDAC and disease evolution are not available. The dysregulation of microRNAs (miRNAs) has been associated with cancer development and progression, and some miRNAs have been reported to promote specific metastasis. In this study we aimed to identify the miRNAs dysregulated in PDAC tumoral tissues and a subset of miRNAs associated with tumoral characteristics, mainly metastasis presence and site. For this, the expression of 84 miRNAs was evaluated by qPCR in 30 tumoral tissues and 16 samples of non-tumoral pancreatic tissues. The comparison revealed 32 dysregulated miRNAs (19 upregulated and 13 downregulated) in the PDAC group. Reactome pathway over-representation analysis revealed that these miRNAs are involved in several biological pathways, including “ESR-mediated signaling”, “PIP3 activates AKT signaling”, and “Regulation of PTEN”, among others. Moreover, our study identified an upregulation of miR-15b-5p and miR-20b-5p in the tumoral tissues of patients with hepatic metastasis, outlining these miRNAs as potential markers for hepatic metastasis. No significant difference in miRNA expression was observed in relation to anatomic location, lymphovascular invasion, lung metastasis, and the presence of diabetes.
... 3 Anticancer mechanisms of icariin 3.1 Lung cancer As the leading cause of cancer-related mortality worldwide, lung cancer is characterized by drug resistance and poor prognosis (Zhu and Ren, 2022). Traditional first-line chemotherapeutic drugs are frequently accompanied by serious side effects when used to treat tumors (Rawal et al., 2023). ...
... They found that icariin could suppress lung cancer progression via the miR-205-5p/PTEN and PI3K/Akt signaling pathways in vivo and in vitro in a time-and dose-dependent manner. More importantly, icariin had hardly any toxic effect on (Zhu and Ren, 2022). An experiment by Han et al. also demonstrated the inhibitory effect of the miR-370 signaling pathway on lung cancer via downregulating PIM1. ...
... Although the therapeutic efficacy of icariin has not been fully confirmed, some cellular and animal experimental studies have demonstrated that icariin may inhibit the growth, invasion, drug resistance of tumor cells, and induce the apoptosis of tumor cells through multiple pathways. Importantly, icarinn has no toxic side effects on normal cells (Zhu and REN, 2022;Liu et al., 2023b). Additionally, icariin can synergistically enhance the therapeutic effects of conventional chemotherapeutic drugs and increase the sensitivity of cancer cells to chemotherapeutic drugs (Zhai et al., 2021). ...
Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.
... Icariin (ICA), a flavonoid derived from Epimedium, exerts anti-inflammatory, 8 antioxidant, and neuroprotective effects. 9,10 ICA inhibited the growth of cancer cells, such as ovarian cancer, 11 cervical cancer, 12 gastric cancer, 13 lung cancer, 14 and breast cancer. 15 ICA has been used clinically as an anticancer agent against a broad range of cancers. ...
Background
Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive.
Methods
The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc.
Results
This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox‐induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway.
Conclusion
We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.
... The reduction of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways upon icariin administration leads to the alleviation of cervical cancer [97]. In lung cancer, it is demonstrated that icariin is able to target the miR-205-5p/PTEN axis leading to the modulation of the PI3K/Akt signaling pathway and inhibition of tumor progression [98]. The activation of the mitochondrial apoptotic pathway is reported as another mechanism that enables icariin to treat lung cancer [99]. ...
Ovarian cancer is described as one of the most common types of cancer and the leading cause of cancer-related deaths due to the high aggressiveness of this malignancy. However, the current therapeutically strategies failed to confront ovarian cancer or are accompanied by significant adverse effects leading to the recurrence of the disease and/or affecting the quality of life of survivors. On the other hand, ovarian cancer is recognized as a heterogenous disorder that is specified by alteration in a variety of molecular and cellular markers. Thereby, researchers are keen to find a novel therapeutical strategy representing high efficacy and safety, as well as be able to modulate altered biomolecules and signaling pathways. Icariin is a phytoestrogen with desired properties that are suggested for several chronic complications, particularly different types of cancer. The aim of the present study was to reveal the ameliorative characteristics of icariin and then discuss the antitumoral activities of this phytochemical against ovarian cancer with an emphasis on the modified molecular signaling pathways.
Objective
To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.
Methods
We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation. Autophagy expression was analyzed using monodansylcadaverine staining. Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy, pyroptosis, and the mTOR pathway. Cellular damage was examined using the lactate dehydrogenase assay. Moreover, cathepsin B and NLRP3 were detected by co-immunoprecipitation.
Results
Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy. The levels of LC3-II/LC3-I and beclin-1 were increased, while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol. These changes were reversed upon overexpression of mTOR. Furthermore, 3-methyladenine resulted in a decrease in inflammatory cytokines, pyroptosis-related protein levels, and lactate dehydrogenase concentration, compared to the icariin plus curcumol group. Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.
Conclusions
Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B. These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.
