Influences of Ru and ZrO2 interaction on the hydroesterification of styrene.

Interfacial Lewis acid-base pairs are commonly found in ZrO2-supported metal catalysts due to the facile generation of oxygen vacancies of ZrO2. These pairs have been reported to play a crucial role in olefin hydroesterification, especially in the absence of acid promoters and ligands. In this study, a series of ZrO2-supported Ru catalysts with ruthenium(iii) chloride and ruthenium(iii) acetylacetonate as precursors were prepared for the styrene hydroesterification. The catalysts were thoroughly characterized by TPR, TEM, EPR, XPS, and FTIR. The Ru precursors significantly influenced the size and electronic properties of Ru clusters, albeit having minimal impact on oxygen vacancies. Mechanistic studies of styrene hydroesterification over ZrO2-supported Ru catalysts revealed that the carbon monoxide insertion followed the hydrogen transfer step to activated styrene. Higher activity is exhibited over ZrO2-supported Ru catalysts prepared with ruthenium(iii) chloride as a precursor, attributed to the lower adsorption strength of CO over Ru clusters, as evidenced by FTIR and DFT calculations.

Comprehensive multi-omics analysis of resectable locally advanced gastric cancer: Assessing response to neoadjuvant camrelizumab and chemotherapy in a single-center, open-label, single-arm phase II trial.

BACKGROUND: The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. METHODS: A single-arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi-omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Multi-omics analysis was assessed by whole-exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre- and post-neoadjuvant therapy. RESULTS: This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment-emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi-omics analysis correlated with treatment response, highlighting associations between HER2-positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post-treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. CONCLUSION: The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

Genetic lineage tracing reveals stellate cells as contributors to myofibroblasts in pancreas and islet fibrosis.

Pancreatic stellate cells (PSCs) are suggested to play an important role in the development of pancreas and islet fibrosis. However, the precise contributions and solid in vivo evidence of PSCs to the fibrogenesis remain to be elucidated. Here, we developed a novel fate-tracing strategy for PSCs by vitamin A administration in Lrat-cre; Rosa26-tdTomato transgenic mouse. The results showed that stellate cells give rise to 65.7% of myofibroblasts in cerulein-induced pancreatic exocrine fibrosis. In addition, stellate cells in islets increase and contribute partly to myofibroblasts pool in streptozocin-induced acute or chronic islet injury and fibrosis. Furthermore, we substantiated the functional contribution of PSCs to fibrogenesis of pancreatic exocrine and islet in PSCs ablated mice. We also found stellate cells' genetic ablation can improve pancreatic exocrine but not islet fibrosis. Together, our data indicates that stellate cells are vital/partial contributors to myofibroblasts in pancreatic exocrine/islet fibrosis.

Uncovering the Mechanism of the Role of Fly Ash in the Self-Healing Ability of Mortar with Different Curing Ages.

As an admixture of cement-based materials, the reaction of fly ash (FA) usually takes place in the late age of curing, so FA will affect the self-healing ability of long-age cement-based materials. The self-healing potential and the characteristics of self-healing products of cementitious materials before and after crack healing were analyzed by microscopic tests, and the mechanism of the effect of fly ash on the self-healing performance of cementitious materials was revealed. The results showed that the increase in fly ash content promoted the improvement of the self-repair performance of cracked specimens at 28 d, especially when the fly ash dosage was 40%, the crack opened after 30 d of healing in water was completely closed, the UPV value after recovery was close to 3000 m/s, the self-repair efficiency of maximum amplitude and main frequency amplitude was up to more than 60%, and the recovery rate of compressive strength was increased to more than 30%. However, the increase in fly ash content was not conducive to the self-repair of cracked samples at 210 d, and with the increase in fly ash content, the crack closure effect weakened, the UPV value after recovery decreased, the crack repair rate based on ultrasonic transmission decreased to about 20%, and the compressive strength recovery rate increased slightly. In addition, calcium carbonate precipitation was the main repair product of crack filling and healing, including calcite and spherulite. With the increase in fly ash content, the content of element C in the self-repair products of 28-day-old specimens gradually increased, and the size of calcium carbonate crystals gradually decreased, but the filling was denser, whereas the calcium carbonate crystals in the self-repair products of 210 d specimens gradually became fine and loose.

The Synergistic Effects of Ultrafine Slag Powder and Limestone on the Rheology Behavior, Microstructure, and Fractal Features of Ultra-High Performance Concrete (UHPC).

This study investigated the effect of the interaction between ultrafine slag powder (USL) and limestone (LS) on the rheology behavior, microstructure, and fractal features of UHPC. The results indicated that B2 with mass ratio of 2:1 between the USL and LS obtained the highest compressive strength and the lowest yield stress. The combination of the USL and LS facilitated the cement hydration, ettringite, and monocarboaluminate (Mc) formation, as well as the increase in the polymerization of the C-S-H. The synergistic action between the USL and LS refined the pore structure due to the formation of the Mc, compensating for the consumption of the CH by the pozzolanic reaction, which provided a denser microstructure in the UHPC. The fractal dimension (Ds) of the UHPC was strongly related to the concrete pore structures and the compressive strength, which demonstrated that a new metric called the Ds value may be used to assess the synergistic effect of the UHPC.

Long-term exercise preserves pancreatic islet structure and ß-cell mass through attenuation of islet inflammation and fibrosis.

Islet fibrosis is associated with the disruption of islet structure and contributes to ß-cell dysfunction, playing an essential role in the pathogenesis of type 2 diabetes. Physical exercise has been shown to attenuate fibrosis in various organs; however, the effect of exercise on islet fibrosis has not been defined. Male Sprague-Dawley rats were divided into four groups: normal diet sedentary [N-Sed], normal diet + exercise [N-Ex], high-fat diet sedentary [H-Sed], and high-fat diet + exercise [H-Ex]. After 60 weeks of exercise, 4452 islets from Masson-stained slides were analyzed. Exercise led to a 68% and 45% reduction in islet fibrosis in the normal and high-fat diet groups and was correlated with a lower serum blood glucose. Fibrotic islets were characterized by irregular shapes and substantial loss of ß-cell mass, which were significantly reduced in the exercise groups. Remarkably, the islets from exercised rats at week 60 were morphologically comparable to those of sedentary rats at 26 weeks. In addition, the protein and RNA levels of collagen and fibronectin, and the protein levels of hydroxyproline in the islets were also attenuated by exercise. This was accompanied by a significant reduction in inflammatory markers in the circulation Interleukin-1 beta (IL-1ß)] and pancreas [IL-1ß, Tumor Necrosis Factor-alpha, Transforming Growth Factor-ß, and Phosphorylated Nuclear Factor Kappa-B p65 subunit], lower macrophage infiltration, and stellate cell activation in the islets of exercised rats. In conclusion, we have demonstrated that long-term exercise preserves pancreatic islet structure and ß-cell mass through anti-inflammatory and anti-fibrotic actions, suggesting additional rationales for the success of exercise training in the prevention and treatment of type 2 diabetes that should be further explored.

Graphene oxide leads to mitochondrial-dependent apoptosis by activating ROS-p53-mPTP pathway in intestinal cells.

Owing to its unique physical and chemical properties, graphene oxide (GO) has a wide range of applications in biomedical field. However, with the gradual improvement of biosafety investigations on nanomaterials, growing literatures have pointed out that GO could lead to oxidative stress, aggravation of inflammatory responses, and even irreversible lesions in human multi-tissues, while its damage to small intestinal remained unclear. In this study, we conducted an in-depth study on the toxicological effect of GO on intestinal tissues, and further clarified its toxic effect and molecular mechanism on inducing intestinal cell death. Firstly, we characterized the shape size, potential value, Fourier Transform infrared spectroscopy (FT-IR) characterization and pro-oxidant properties of GO nanosheets. The cytotoxicity of different concentrations of GO to Caco-2 and IEC-6 cell lines was thereafter observed, which was specifically manifested as invoking NADPH Oxidase 1 (NOX1) proteins, accompanied generation of reactive oxygen species (ROS). Since that, more p53 flowed into mitochondria to combine with cyclophilin D (CYPD), thus induced mitochondrial permeability transition pore (mPTP) opening. Through ROS-CyPD-mPTP signaling pathway, GO exerted imbalance of mitochondrial homeostasis, while released cytochrome c (CytC) would ultimate caspase-dependent cell apoptosis. In vivo experiment also confirmed that the microstructure of small intestine was damaged, and the apoptosis rate and oxidative markers were significantly increased in GO-treated Sprague- Dawley (SD) rats (40 mg/kg once every other day from day 1 to day 9 by oral gavage). Based on these findings, we conclude that the adverse effects of oral exposure of GO on the biological system mainly concentrate in the digestive tract, and clarify the key role of ROS-mitochondrial homeostasis-apoptosis axis in GO-derived intestinal toxicity. Considering all these results and the fact that GO exhibited intestinal toxicity, we believe that this research providing a safety reference for its biomedical applications.

Effect of Graphene Oxide on Properties of Alkali-Activated Slag.

Alkali-activated materials, a new kind of low-carbon cement, have received extensive attention. While in order to obtain excellent functions, the modification of alkali-activated materials by nano-materials has become one of the important research directions of alkali-activated materials. Therein, the hydration property, mechanical properties, and action mechanism of the alkali-activated slag with and without graphene oxide (GO) were analyzed and evaluated. Results showed the compressive strength of mortar decreased at 3 days and 28 days by adding GO. While the flexural strength of mortar cured for different ages increased with increasing GO content, and the flexural strength increasing rate reached up to 15.94% at 28 days, thus, the toughening effect of GO was significant. GO accelerated the hydration process of alkali-activated slag because the functional groups offered nucleation sites to induce the generation of more hydration products. Furthermore, the addition of GO increased the number of harmless pores and reduced the pore size, but also introduced a large number of harmful pores, resulting in the reduction of compressive strength.

Screening and Identification of Key Genes for Activation of Islet Stellate Cell.

Background: It has been demonstrated that activated islet stellate cells (ISCs) play a critical role in islet fibrogenesis and significantly contribute to the progression of type 2 diabetes mellitus. However, the key molecules responsible for ISCs activation have not yet been determined. This study aimed to identify the potential key genes involved in diabetes-induced activation of ISCs. Method: Stellate cells were isolated from three 10-week-old healthy male Wistar rats and three Goto-Kakizaki (GK) rats. Cells from each rat were primary cultured under the same condition. A Genome-wide transcriptional sequence of stellate cells was generated using the Hiseq3000 platform. The identified differentially expressed genes were validated using quantitative real-time PCR and western blotting in GK rats, high fat diet (HFD) rats, and their controls. Results: A total of 204 differentially expressed genes (DEGs) between GK. ISCs and Wistar ISCs (W.ISCs) were identified, accounting for 0.58% of all the 35,362 genes detected. After the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the mRNA levels of these genes were further confirmed by real-time PCR in cultured ISCs. We then selected Fos, Pdpn, Bad as the potential key genes for diabetes-induced activation of ISCs. Finally, we confirmed the protein expression levels of FOS, podoplanin, and Bad by western blotting and immunofluorescence in GK rats, HFD rats, and their controls. The results showed that the expression level of FOS was significantly decreased, while podoplanin and Bad were significantly increased in GK.ISCs and HFD rats compared with controls, which were consistent with the expression of α-smooth muscle actin. Conclusions: A total of 204 DEGs were found between the GK.ISCs and W.ISCs. After validating the expression of potential key genes from GK rats and HFD rats, Fos, Pdpn, and Bad might be potential key genes involved in diabetes-induced activation of ISCs.

Prognostic Value of Podoplanin in Various Tumors.

BACKGROUND: The prognostic significance of podoplanin (PDPN) in tumor cells for cancer patients' survival remains controversial. Therefore, we performed this meta-analysis to clarify the relationship between the podoplanin-positive tumor cells and cancer prognosis. METHOD: Eligible studies were identified by searching the Pubmed and EBSCO online databases up to August 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the correlation between podoplanin expression and overall survival (OS) and/or disease-free survival (DFS) and odds ratios (ORs) with 95% CIs severed as the summarized statistics for clinicopathological characteristic. RESULTS: A total of 2155 patients from 21 eligible studies were included. The results revealed that high expression of podoplanin was associated with a poor survival rate in cancer patients. Further subgroup analysis stratified by tumor type showed that podoplanin-positive tumor cell infiltration had a negative prognostic effect associated with survival in esophageal cancer and oropharyngeal cancer. In addition, high expression of these cells was significantly associated with N stage, T stage, TNM stage and vascular invasion. CONCLUSION: Our study suggests the over-expression of podoplanin might be a significant prognostic indicator for patients with esophageal and oropharyngeal cancer.

Mesenchymal stem cell-derived exosomal miR-146a reverses diabetic ß-cell dedifferentiation.

BACKGROUND: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating type 2 diabetes mellitus (T2DM) in clinical studies. Accumulating evidence has suggested that the therapeutic effects of MSCs are not due to their direct differentiation into functional ß-cells but are instead mediated by their paracrine functions. Among them, exosomes, nano-sized extracellular vesicles, are important substances that exert paracrine functions. However, the underlying mechanisms of exosomes in ameliorating T2DM remain largely unknown. METHODS: Bone marrow mesenchymal stem cell (bmMSC)-derived exosomes (bmMDEs) were administrated to T2DM rats and high-glucose-treated primary islets in order to detect their effects on ß-cell dedifferentiation. Differential miRNAs were then screened via miRNA sequencing, and miR-146a was isolated after functional verification. TargetScan, reporter gene detection, insulin secretion assays, and qPCR validation were used to predict downstream target genes and involved signaling pathways of miR-146a. RESULTS: Our results showed that bmMDEs reversed diabetic ß-cell dedifferentiation and improved ß-cell insulin secretion both in vitro and in vivo. Results of miRNA sequencing in bmMDEs and subsequent functional screening demonstrated that miR-146a, a highly conserved miRNA, improved ß-cell function. We further found that miR-146a directly targeted Numb, a membrane-bound protein involved in cell fate determination, leading to activation of ß-catenin signaling in ß-cells. Exosomes derived from miR-146a-knockdown bmMSCs lost the ability to improve ß-cell function. CONCLUSIONS: These findings demonstrate that bmMSC-derived exosomal miR-146a protects against diabetic ß-cell dysfunction by acting on the NUMB/ß-catenin signaling pathway, which may represent a novel therapeutic strategy for T2DM.

Mesenchymal stem cell-conditioned medium alleviates high fat-induced hyperglucagonemia via miR-181a-5p and its target PTEN/AKT signaling.

BACKGROUND: α-cell dysregulation gives rise to fasting and postprandial hyperglycemia in type 2 diabetes mellitus(T2DM). Administration of Mesenchymal stem cells (MSCs) or their conditioned medium can improve islet function and enhance insulin secretion. However, studies showing the direct effect of MSCs on islet α-cell dysfunction are limited. METHODS: In this study, we used high-fat diet (HFD)-induced mice and α-cell line exposure to palmitate (PA) to determine the effects of bone marrow-derived MSC-conditioned medium (bmMSC-CM) on glucagon secretion. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay(ELISA). To investigate the potential signaling pathways, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT and phosphorylated AKT(p-AKT) were assessed by Western blotting. RESULTS: In vivo, bmMSC-CM infusion improved the glucose and insulin tolerance and protected against HFD-induced hyperglycemia and hyperglucagonemia. Meanwhile, bmMSC-CM infusion ameliorated HFD-induced islet hypertrophy and decreased α- and ß-cell area. Consistently, in vitro, glucagon secretion from α-cells or primary islets was inhibited by bmMSC-CM, accompanied by reduction of intracellular PTEN expression and restoration of AKT signaling. Previous studies and the TargetScan database indicate that miR-181a and its target PTEN play vital roles in ameliorating α-cell dysfunction. We observed that miR-181a-5p was highly expressed in BM-MSCs but prominently lower in αTC1-6 cells. Overexpression or downregulation of miR-181a-5p respectively alleviated or aggravated glucagon secretion in αTC1-6 cells via the PTEN/AKT signaling pathway. CONCLUSIONS: Our observations suggest that MSC-derived miR-181a-5p mitigates glucagon secretion of α-cells by regulating PTEN/AKT signaling, which provides novel evidence demonstrating the potential for MSCs in treating T2DM.

Improving the Autogenous Self-Sealing of Mortar: Influence of Curing Condition.

With the construction of projects under severe environments, new and higher requirements are put forward for the properties of concrete, especially the autogenous self-sealing property, which is greatly affected by the curing environment and the state of the water. Herein, six types of curing conditions, including in air with a relative humidity of 30%, 60%, and 95%; flowing water; wet-dry cycles; and static water, are designed to investigate the autogenous self-sealing of mortar under different curing conditions. The results showed that the self-sealing ratios are higher than 60% and the cracks are closed for the mortar undergoing the wet-dry cycles and the static water. However, the self-sealing ratios of mortar are lower than 10% and the cracks are almost unchanged when the mortar is cured in the air with a relative humidity (RH) of 30% and 60%. The static liquid water is more conducive to the continued hydration of cement and the formation of CaCO3 than the flowing water. The research provides guidance for the design of concrete and the improvement of autogenous self-sealing when the concrete serves in different environments.

REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity.

Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking1,2. The molecular mechanism that underlies this temporal pattern is unclear. Here we show that the nuclear receptors REV-ERB-α and REV-ERB-ß (referred to here as 'REV-ERB') in the GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviours during regular light-dark cycles. REV-ERB regulates the rhythmic expression of genes that are involved in neurotransmission in the SCN, and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at waking leads to glucose intolerance, whereas restoration of the temporal pattern of either SCNGABA neuron firing or REV-ERB expression rescues the time-dependent glucose metabolic phenotype caused by REV-ERB depletion. In individuals with diabetes, an increased level of blood glucose after waking is a defining feature of the 'extended dawn phenomenon'3,4. Patients with type 2 diabetes with the extended dawn phenomenon exhibit a differential temporal pattern of expression of REV-ERB genes compared to patients with type 2 diabetes who do not have the extended dawn phenomenon. These findings provide mechanistic insights into how the central circadian clock regulates the diurnal rhythm of hepatic insulin sensitivity, with implications for our understanding of the extended dawn phenomenon in type 2 diabetes.

Separation of N'-nitrosonornicotine isomers and enantiomers by supercritical fluid chromatography tandem mass spectrometry.

N'-nitrosonornicotine (NNN) is one of the most prevalent and toxic tobacco-specific nitrosoamines. A chiral center at its 2'-position results in R and S enantiomers, the partial double bond character of the NN = O group also results in E and Z isomers, therefore, NNN can form a total of four absolute configurations (E-(R)-NNN, E-(S)-NNN, Z-(R)-NNN, and Z-(S)-NNN). This study investigated the resolution of R/S enantiomers and E/Z isomers of NNN by supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS). The baseline separation of E/Z-(R,S)-NNN isomers/enantiomers was accomplished through the optimization of chiral columns and co-solvents. Due to the lack of single standard of E/Z isomers, only R-NNN (sum of E-(R)-NNN and Z-(R)-NNN) and S-NNN (sum of E-(S)-NNN and Z-(S)-NNN) were further examined. Through the comprehensive optimization of SFC-MS/MS conditions, R-NNN and S-NNN were separated with a run time of 5 min, the developed method was validated, and its applicability to the determination of NNN enantiomers in burley tobacco samples was demonstrated. This study could be applied to preparative separation of single enantiomer and/or isomer of NNN, and could provide potential benefits to biologic activity studies on these enantiomers and isomers.

Long Non-coding RNA LINC00115 Contributes to the Progression of Colorectal Cancer by Targeting miR-489-3p via the PI3K/AKT/mTOR Pathway.

Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.