RNF114 facilitates the proliferation, stemness, and metastasis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), the fourth of the world's major common malignancy, poses a serious threat to the physical and mental health of the population. Nevertheless, the prognosis of CRC patients remains unsatisfactory. Consequently, it is still imperative to continuously discover the CRC mechanisms. METHODS: The expression profiles of mRNAs were recognized by whole transcriptome sequencing to identity differentially expressed mRNA (DE-mRNA). TCGA COAD cohort, PPOGgene and Kaplan-Meier Plotter databases were utilized to validate RNF114 relevance to CRC prognosis. The effect of RNF114 on the malignant biological behavior of CRC was explored in CRC cells and subcutaneous tumor models and lung metastasis model after exogenous regulation of RNF114. RESULTS: A total of 1358 DE-mRNAs were identified, including 617 up-regulated and 741 down-regulated DE-mRNAs, and they were mainly involved in the term of receptor ligand activity, Wnt signaling pathway and pathway in cancer. Notably, RNF114 was hyper-expressed in tissues and cell of CRC, and significantly correlated with tumor invasion depth and TNM stage of CRC patients. RNF114 expression were significantly associated with overall survival, and had superior diagnostic value in CRC. In vitro, knockdown of RNF114 statistically diminished the proliferation, stemness, invasion and wound healing of CRC cells and facilitated their apoptosis, and the opposite result was observed for overexpression of RNF114. In vivo, knockdown of RNF114 effectively diminished the mass and volume of tumors, and lung metastasis in animal model. CONCLUSIONS: In summary, we identified DE-mRNAs in CRC, and elucidated that RNF114 facilitates CRC process. The discovery will contribute to theoretical foundation for RNF114 as a potential therapeutic target and biomarker, and offer new perspectives for CRC research.

High-Output Lotus-Leaf-Bionic Triboelectric Nanogenerators Based on 2D MXene for Health Monitoring of Human Feet.

As versatile energy harvesters, triboelectric nanogenerators (TENGs) have attracted considerable attention in developing portable and self-powered energy suppliers. The question of how to improve the output power of TENGs using cost-effective means is still under vigorous investigation. In this paper, high-output TENGs were successfully produced by using a simple and low-cost lotus-leaf-bionic (LLB) method. Well-distributed microstructures were fabricated via the LLB method on the surface of a polydimethylsiloxane (PDMS) negative triboelectric layer. 2D MXene (Ti3C2Tx) and graphene were doped into the structured PDMS to evaluate their effects on the performance of TENG. Owing to merits of the MXene doping and microstructures on the PDMS surface, the output power of MXene-doped LLB TENGs reached as high as 104.87 W/m2, which was about 10 times higher than that of graphene-doped devices. The MXene-doped LLB TENGs can be used as humidity sensors, with a sensitivity of 4.4 V per RH%. In addition, the MXene-doped LLB TENGs were also sensitive to human body motions; hence, a foot health monitoring system constructed by the MXene-doped LLB TENGs was successfully demonstrated. The results in this work introduce a way to produce cost-effective TENGs using bionic means and suggest the promising applications of TENGs in the smart monitoring system of human health.

Flexible Threshold Switching Based on CsCu2I3 with Low Threshold Voltage and High Air Stability.

Halide perovskites featuring remarkable optoelectronic properties hold great potential for threshold switching devices (TSDs) that are of primary importance to next-generation memristors and neuromorphic computers. However, such devices are still in their infancy due to the unsolved challenges of high threshold voltage, poor stability, and lead-containing features. Herein, a unipolar TSD based on an all-inorganic halide perovskite of CsCu2I3 is demonstrated, exhibiting the fascinating attributes of a low threshold voltage of 0.54 V, a high ON/OFF ratio of 104, robust air stability over 70 days, a steep switching slope of 6.2 mV·decade-1, and lead-free composition. Moreover, the threshold voltage can be further reduced to 0.23 V using UV illumination to reduce the barrier of iodide ion migration. The multilevel threshold switching behavior can be realized through the modulation of either the compliance current or the scan rate. The TSD with mechanical compliance and transparency is also demonstrated. This work enriches TSDs with expanded perovskite materials, boosting the related applications of this emerging class of device families.

Systemic inflammation-based predictors of pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.

Aim: To investigate whether systemic inflammation-based predictors can predict tumor response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Materials and Methods: Totally, 205 LARC patients undergoing neoadjuvant CRT and curative surgery between 2008 and 2017 were analyzed. After propensity score matching, 132 patients were included in the study. Hematological parameters were collected, and their relationship with tumor response was investigated. Results: After propensity score matching, patients in good response group before CRT displayed significantly lower neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) than those in poor response group, while there were no significant differences in all hematological characteristics between the two groups after CRT. The cutoff values of pre-CRT NLR and pre-CRT PLR after receiver operating characteristic analysis were 3.10 and 198.7, respectively. Multivariate analysis revealed that while there was no association between pre-CRT PLR and tumor response, pre-CRT NLR ≥3.1 was identified as the predictor of poor tumor response (P = 0.007). Conclusion: An increased NLR before CRT can serve as a hematological factor for predicting a poor tumor response in LARC.

Bimodal Tactile Sensor without Signal Fusion for User-Interactive Applications.

Tactile sensors with multimode sensing ability are cornerstones of artificial skin for applications in humanoid robotics and smart prosthetics. However, the intuitive and interference-free reading of multiple tactile signals without involving complex algorithms and calculations remains a challenge. Herein a pressure-temperature bimodal tactile sensor without any interference is demonstrated by combining the fundamentally different sensing mechanisms of optics and electronics, enabling the simultaneous and independent sensing of pressure and temperature with the elimination of signal separation algorithms and calculations. The bimodal sensor comprises a mechanoluminescent hybrid of ZnS-CaZnOS and a poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) thermoresistant material, endowing the unambiguous transduction of pressure and temperature into optical and electrical signals, respectively. This device exhibits the highest temperature sensitivity of -0.6% °C-1 in the range of 21-60 °C and visual sensing of the applied forces at a low limitation of 2 N. The interference-free and light-emitting characteristics of this device permit user-interactive applications in robotics for encrypted communication as well as temperature and pressure monitoring, along with wireless signal transmission. This work provides an unexplored solution to signal interference of multimodal tactile sensors, which can be extended to other multifunctional sensing devices.

Long non-coding RNA PCED1B antisense RNA 1 promotes gastric cancer progression via modulating microRNA-215-3p / C-X-C motif chemokine receptor 1 axis.

Long non-coding RNAs (lncRNAs) emerge as vital modulators and tissue-specific biomarkers of multiple cancers, including gastric cancer (GC). Instead, the expression characteristics, biological function and molecular mechanism of lncRNA PCED1B antisense RNA 1 (PCED1B-AS1) in GC await more elaboration. In this study, 48 cases of GC tissues and matched non-cancerous tissues were collected, and PCED1B-AS1, microRNA-215-3p (miR-215-3p) and C-X-C motif chemokine receptor 1 (CXCR1) expression levels were detected by qRT-PCR. Besides, CCK-8, EdU, Transwell and Western blot assays were conducted to assess the impact of PCED1B-AS1 or miR-215-3p on cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). The interaction between genes was verified by bioinformatics analysis, rna immunoprecitipation (RIP) and dual-luciferase reporter gene assays. We demonstrated that, PCED1B-AS1 expression level was raised in GC tissues and cell lines, and increased expression of PCED1B-AS1 was in association with tumor size, TNM stage and lymph node metastasis in GC patients. Additionally, PCED1B-AS1 overexpression promoted GC cells proliferation, migration, invasion and EMT, and miR-215-3p overexpression counteracted the biological effects of PCED1B-AS1. Mechanistically, PCED1B-AS1 specifically inhibited miR-215-3p expressions, thus up-regulating CXCR1 expressions. In conclusion, PCED1B-AS1 accelerates GC progression via adsorbing miR-215-3p and up-regulating CXCR1, indicating that PCED1B-AS1 is a novel therapeutic target for treating GC.

miR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer.

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer.

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Discovery of novel isoliquiritigenin analogue ISL-17 as a potential anti-gastric cancer agent.

Isoliquiritigenin (ISL), a natural product isolated from licorice root, exhibits anti-gastric cancer effects. However, applications of ISL are still limited in clinical practice due to its poor bioavailability. To discovery of more effective anti-gastric cancer agents based on ISL, aldol condensation reaction was applied to synthesize the ISL analogues. MTS assay was used to evaluate the inhibitory activities of ISL analogues against SGC-7901, BGC-823 and GES-1 cells in vitro. Cell cycle distribution, apoptosis and reactive oxygen species (ROS) generation were detected by flow cytometry. Western blot assay was used to analyze the expression levels of related proteins. The drug-likeness and pharmacokinetic properties were predicted with Osiris property explorer and PreADMET server. As a result, 18 new ISL analogues (ISL-1 to ISL-18) were synthesized. Among these analogues, ISL-17 showed the strongest inhibitory activities against SGC-7901 and BGC-823 cells, and could induce G2/M cell cycle arrest and apoptosis in these two cell lines. Treatment with ISL-17 resulted in increased ROS production and elevated autophagy levels in SGC-7901 cells. The PI3K/AKT/mTOR signaling pathway was down-regulated after treatment with ISL-17 in SGC-7901 cells. The results of drug-likeness and pharmacokinetic prediction indicated that all the ISL analogues complied with Lipinski's rule of five and Veber rule and had a favorable ADME character. Overall, our results attest that ISL-17 holds promise as a candidate agent against gastric cancer.

Comprehensive Analysis of the Expression Profiles of Long Non-Coding RNAs with Associated ceRNA Network Involved in the Colon Cancer Staging and Progression.

Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete with microRNAs (miRNAs) in cancer occurrence and development. However, the differential expression of RNAs and their ceRNA network during the development of colon cancer (CC) remains unclear. This study was aimed at comprehensive analysis of the lncRNAs and their ceRNA networks associated with CC. Whole transcriptome sequencing was performed on colorectal and adjacent normal tissues at different pathological stages. Forty-nine lncRNAs were differently expressed between the CC tissues and their adjacent normal tissues at all stages. Aberrant expression of lncRNA CDKN2B-AS1 and lncRNA MIR4435-2HG was confirmed by TCGA database. Moreover, 14 lncRNAs were differentially expressed between early and advance stages of the tumor tissues, and 117 miRNAs were specifically expressed in stage III & IV. Weighted gene co-expression network analysis of 17105 differently expressed mRNAs revealed that the mRNAs shown in module pink, midnight blue, black, and light cyan were related to TNM and pathological stage, and that these mRNAs were enriched in cancer related functions and pathways. As DElncRNA showed a trend of change similar to that of the DEmRNA and opposite to that of DEmiRNA, ceRNA network was constructed with 3 DEmiRNAs, 5 DElncRNAs, and 130 DEmRNAs. Real time PCR revealed that expression of MEG3 was decreased in the tumor tissues belonging to stage III and IV as compared to that in stage I. Moreover, hsa-miR-324-5p was upregulated, while FGFR3, PLCB4, and IKBKB were downregulated in the tumor tissues as compared to that in the adjacent normal tissues. Thus, this study revealed differentially expressed lncRNA between different stages of CC as well as suggested that lncRNA CDKN2B-AS1, MIR4435-2HG, and MEG3 may act as diagnostic biomarkers for the development of CC.

Polyclonal Rabbit Anti-Cancer-Associated Fibroblasts Globulins Induce Cancer Cells Apoptosis and Inhibit Tumor Growth.

Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. CAFs regulated the growth and development, invasion and metastasis of primary tumors, as well as response to treatment. Recent studies indicated that monoclonal antibody therapies had limited success, thus more effective polyclonal antibodies (Poly Abs) is urgently needed. Poly Abs is a possible alternative because they target multiple antigens simultaneously. In this report, we prepared Poly Abs by immunizing rabbits with the bFGF-activated fibroblasts. The Poly Abs inhibited the cancer cells proliferation as revealed by MTT analysis. The Poly Abs induced apoptosis as indicated by flow cytometric analysis, and microscopic observation of apoptotic changes in morphology. Compared with the control IgG, Poly Abs significantly inhibited tumor cells migration as indicated by wound healing and transwell analysis in vitro, and lung metastasis analysis in vivo. Serial intravenous injections of Poly Abs inhibited tumor growth in mice bearing murine CT26 colon carcinoma. Ki67 analysis indicated that Poly Abs significantly inhibited tumor cells proliferation, as compared to control Ig G treatments. Our findings suggested that Poly Abs was an effective agent for apoptosis induction, migration and metastasis inhibition. The Poly Abs may be useful as a safe anticancer agent for cancer immunotherapy in the future.

[Inhibitory effect of apatinib on HCT-116 cells and its mechanism].

OBJECTIVE: To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved. METHODS: The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting. RESULTS: Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an IC50 value of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes. CONCLUSION: Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.