Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity.

Cardiovascular diseases, particularly those involving arterial stenosis and smooth muscle cell proliferation, pose significant health risks. This study aimed to investigate the therapeutic potential of curcumol in inhibiting platelet-derived growth factor-BB (PDGF-BB)-induced human aortic smooth muscle cell (HASMC) proliferation, migration and autophagy. Using cell viability assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays and Western Blot analyses, we observed that curcumol effectively attenuated PDGF-BB-induced HASMC proliferation and migration in a concentration-dependent manner. Furthermore, curcumol mitigated PDGF-BB-induced autophagy, as evidenced by the downregulation of LC3-II/LC3-I ratio and upregulation of P62. In vivo experiments using an arteriosclerosis obliterans model demonstrated that curcumol treatment significantly ameliorated arterial morphology and reduced stenosis. Additionally, curcumol inhibited the activity of the KLF5/COX2 axis, a key pathway in vascular diseases. These findings suggest that curcumol has the potential to serve as a multi-target therapeutic agent for vascular diseases.

Murine double minute 2-mediated estrogen receptor 1 degradation activates macrophage migration inhibitory factor to promote vascular smooth muscle cell dedifferentiation and oxidative stress during thoracic aortic aneurysm progression.

Estrogen receptor 1 (ESR1) has been recently demonstrated as a potential diagnostic biomarker for thoracic aortic aneurysm (TAA). However, its precise role in the progression of TAA remains unclear. In this study, TAA models were established in ApoE-knockout mice and primary mouse vascular smooth muscle cells (VSMCs) through treatment with angiotensin (Ang) II. Our findings revealed a downregulation of ESR1 in Ang II-induced TAA mice and VSMCs. Upregulation of ESR1 mitigated expansion and cell apoptosis in the mouse aorta, reduced pathogenetic transformation of VSMCs, and reduced inflammatory infiltration and oxidative stress both in vitro and in vivo. Furthermore, we identified macrophage migration inhibitory factor (MIF) as a biological target of ESR1. ESR1 bound to the MIF promoter to suppress its transcription. Artificial MIF restoration negated the mitigating effects of ESR1 on TAA. Additionally, we discovered that murine double minute 2 (MDM2) was highly expressed in TAA models and mediated protein degradation of ESR1 through ubiquitination modification. Silencing of MDM2 reduced VSMC dedifferentiation and suppressed oxidative stress. However, these effects were reversed upon further silencing of ESR1. In conclusion, this study demonstrates that MDM2 activates MIF by mediating ESR1 degradation, thus promoting VSMC dedifferentiation and oxidative stress during TAA progression.

[Retracted] Rapamycin suppresses the PI3K/AKT/mTOR signaling pathway by targeting SIRT1 in esophageal cancer.

[This retracts the article DOI: 10.3892/etm.2021.10624.].

Rapamycin suppresses the PI3K/AKT/mTOR signaling pathway by targeting SIRT1 in esophageal cancer.

Rapamycin, a secondary metabolite produced by Streptomyces hygroscopicus, is known for its pharmacological effects, especially antitumor and immunosuppressive activities. However, the antitumoral effects of rapamycin in human esophageal cancer (EC) are still poorly understood. To investigate the potential of rapamycin in EC treatment, sirtuin 1 (SIRT1) mRNA expression was quantified in the tissue of patients with EC or in EC cell lines using reverse transcription-quantitative PCR. The protein levels of SIRT1 and PI3K/AKT/mTOR were measured via western blotting. Furthermore, cell viability, migration and invasion were investigated by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The present results suggested that SIRT1 expression was upregulated in EC. In vitro, the inhibitory effect of rapamycin on cell viability in EC was strengthened or weakened after small interfering (si)-SIRT1 or pcDNA3.1/SIRT1 transfection. Furthermore, SIRT1 rescued the inhibitory effect of rapamycin on the migration and invasion of EC cells. In vivo, si-SIRT1 or SIRT1 overexpression in mice could enhance or rescue the inhibitory effects of rapamycin on tumor growth. In addition, SIRT1 transfection rescued the decreased level of phosphorylated (p)-PI3K, p-AKT and p-mTOR induced by rapamycin treatment. Taken together, the present results suggested that rapamycin suppressed the cell viability, migration, invasion and PI3K/AKT/mTOR signaling pathway in EC by negatively regulating SIRT1.

Inhibitory Effect of Selenium on Esophagus Cancer Cells and the Related Mechanism.

Selenium has been associated with many malignant tumors including esophagus cancer (EC). In current study, we examined the effects of three types of selenium, sodium selenite (SSE), methylseleninic acid (MSA) and methylselenocysteine (MSC) on EC cell line Eca109. Here, selenium attenuated cell viability and increased cell apoptosis, especially in MSC, when compared with control group (p<0.05). Meanwhile, MSC and MSA, but no SSE, arrested cell cycle in G0/G1 phase (p<0.05). Mechanistically, FAL1 and PTEN were found to participate in regulating cell cycle and cell apoptosis process by decreasing cyclinD1, CDK2, and promoting caspase-3, caspase-8. In addition, we found that cyclinD1, CDK2 were significantly downregulated by MSA and MSC, while caspase-3, caspase-8 were dramatically upregulated by SSE (p<0.05). Based on these results, we concluded that MSC and MSA inhibit the viability of Eca109 mainly through reducing cell proliferation, while SSE by promoting apoptosis.

Long noncoding RNA PTCSC1 drives esophageal squamous cell carcinoma progression through activating Akt signaling.

Long noncoding RNAs (lncRNAs) have critical roles in various malignancies. However, the specific expression and roles of lncRNA PTCSC1 in esophageal squamous cell carcinoma (ESCC) are still unknown. Here, we identified that lncRNA PTCSC1 was elevated in ESCC tissues and cell lines compared with adjacent noncancerous tissues and normal esophageal epithelial cell line, respectively. Enhanced expression of PTCSC1 facilitated ESCC cells proliferation and migration in vitro and ESCC xenograft growth in vivo. Conversely, deficiency of PTCSC1 suppressed ESCC cells proliferation and migration in vitro and ESCC tumor growth in vivo. Furthermore, PTCSC1 was found to activate Akt signaling in ESCC cells. Blocking Akt signaling with MK-2206 abolished the pro-proliferative and pro-migratory roles of PTCSC1. In summary, our findings demonstrated PTCSC1 as an oncogenic lncRNA in ESCC via activating Akt signaling and suggested that targeting PTCSC1 represents a promising therapeutic strategy against ESCC.

The long noncoding RNA LINC00483 promotes lung adenocarcinoma progression by sponging miR-204-3p.

BACKGROUND: The expression of the long noncoding RNA LINC00483 is upregulated in lung adenocarcinoma (LUAD). However, its role in the progression of LUAD and the underlying mechanisms remain elusive. METHODS: The expressions of LINC00483 and miR-204-3p were determined using quantitative real-time PCR. The correlation between the clinicopathological characteristics of LUAD patients and LINC00483 expression was analyzed using Pearson's χ2 test. A549 and PC-9 cells were transfected with small interfering RNA (siRNA) that specially targeting LINC00483 to assess the impact of its knockdown. Cell proliferation was assessed using the Cell Counting Kit-8 and clone forming assays. Cell migration and cell invasion were evaluated using a transwell assay. The levels of Snail, E-cadherin, N-cadherin and ETS1 proteins were determined via western blotting. The interaction between LINC00483 and miR-204-3p was analyzed using dual-luciferase, fluorescence in situ hybridization and RNA immunoprecipitation. RESULTS: LINC00483 was upregulated in LUAD tissues and cell lines. Higher LINC00483 levels closely correlated to shorter survival times, advanced TNM stage, larger tumor size and positive lymph node metastasis. Cell proliferation, migration and invasion were suppressed after LINC00483 knockdown. LINC00483 mainly localized in the cytoplasm, where it acted as a sponge of miR-204-3p. ETS1 was validated as a downstream target of miR-204-3p and is thus regulated by LINC00483. CONCLUSION: This study demonstrated that LINC00483 facilitates the proliferation, migration and invasion of LUAD cells by acting as a sponge for miR-204-3p, which in turn regulates ETS1.