Mounting evidences indicate that circular RNAs (circRNAs) play vital roles in the development and progression of various cancers. However, the detail functions and underlying mechanisms of circRNAs ...in gastric cancer remain largely unknown.
The expression profile of metastasis-related circRNAs was screened by RNA-seq analysis. qRT-PCR was used to determine the level and prognostic values of circNHSL1 in gastric cancer tissues. In vitro cell wound healing and transwell (migration and invasion) and in vivo tumorigenesis and metastasis assays were performed to evaluate the functions of circNHSL1. Luciferase reporter, RNA immunoprecipitation (RIP) and rescued assays were employed to confirm the interactions between circNHSL1, miR-1306-3p and SIX1. It's widely accepted that as a mesenchymal marker, Vimentin promotes invasion and metastasis in various cancers. Luciferase reporter assay was used to determine the regulation of SIX1 on Vimentin. In addition, In situ hybridization (ISH) was performed to detect the level and prognostic values of miR-1306-3p.
We found that the level of circNHSL1 was significantly up-regulated in gastric cancer, and positively correlated with clinicopathological features and poor prognosis of patients with gastric cancer. Functionally, circNHSL1 promoted cell mobility and invasion, as well as in vivo tumorgenesis and metastasis. Mechanistically, circNHSL1 acted as a miR-1306-3p sponge to relieve the repressive effect of miR-1306-3p on its target SIX1. Moreover, SIX1 enhanced Vimentin expression in the transcriptional level through directly binding to the promoter domain of Vimentin, thereby promoting cell migration and invasion. In addition, miR-1306-3p was down-regulated and negatively correlated with pathological features and poor prognosis in gastric cancer.
CircNHSL1 promotes gastric cancer progression through miR-1306-3p/SIX1/Vimentin axis, and may serve as a novel diagnostic marker and target for treatment of gastric cancer patients.
As a novel type of noncoding RNAs, covalently closed circular RNAs (circRNAs) are ubiquitously expressed in eukaryotes. Emerging studies have related dysregulation of circRNAs to tumorigenesis. ...However, the biogenesis, regulation, function and mechanism of circRNAs in gastric cancer (GC) remain largely unclear.
The expression profile of circRNAs in 6 pairs of GC tissues and adjacent non-tumor tissues was analyzed by RNA-sequencing. Quantitative real-time PCR was used to determine the expression level of circCCDC9 in GC tissues and cell lines. Then, functional experiments in vitro and in vivo were employed to explore the effects of circCCDC9 on tumor growth and metastasis in GC. Mechanistically, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm that circCCDC9 directly sponged miR-6792-3p and alleviated suppression on target CAV1 expression.
Evidently down-regulated expression of circCCDC9 was observed in both GC tissues and cell lines. Expression of circCCDC9 was negatively correlated with tumor size, lymph node invasion, advanced clinical stage and overall survival in GC patients. Functionally, overexpression of circCCDC9 significantly inhibited the proliferation, migration and invasion of GC cell lines in vitro and tumor growth and metastasis in vivo, whereas miR-6792-3p mimics counteracted these effects. Mechanistic analysis demonstrated that circCCDC9 acted as a "ceRNA" of miR-6792-3p to relieve the repressive effect of miR-6792-3p on its target CAV1, then suppressed the tumorigenesis of GC.
CircCCDC9 functions as a tumor suppressor in inhibiting the progression of GC through miR-6792-3p/CAV1 axis, which has provided an exploitable biomarker and therapeutic target for patients with GC.
In this paper, we propose a Circular-ring visual location marker based on a global image-matching model to improve the positioning ability in the fiducial marker system of a single-target mobile ...robot. The unique coding information is designed according to the cross-ratio invariance of the projective theorem. To verify the accuracy of full 6D pose estimation using the Circular-ring marker, a 6 degree of freedom (DoF) robotic arm platform is used to design a visual location experiment. The experimental result shows in terms of small resolution images, different size markers, and long-distance tests that our proposed robot positioning method significantly outperforms AprilTag, ArUco, and Checkerboard. Furthermore, through a repeatable robot positioning experiment, the results indicated that the proposed Circular-ring marker is twice as accurate as the fiducial marker at 2-4 m. In terms of recognition speed, the Circular-ring marker processes a frame within 0.077 s. When the Circular-ring marker is used for robot positioning at 2-4 m, the maximum average translation error of the Circular-ring marker is 2.19, 3.04, and 9.44 mm. The maximum average rotation error is also 1.703°, 1.468°, and 0.782°.
The 3D scanning of a freeform structure relies on the laser probe and the localization system. The localization system, determining the effect of the point cloud reconstruction, will generate ...positioning errors when the laser probe works in complex paths with a fast speed. To reduce the errors, in this paper, a linear laser scanning measurement method is proposed based on binocular vision calibration. A simple and effective eight-point positioning marker attached to the scanner is proposed to complete the positioning and tracking procedure. Based on this, the method of marked point detection based on image moment and the principle of global coordinate system calibration are introduced in detail. According to the invariance principle of space distance, the corresponding points matching method between different coordinate systems is designed. The experimental results show that the binocular vision system can complete localization under different light intensities and complex environments, and that the repeated translation error of the binocular vision system is less than 0.22 mm, while the rotation error is less than 0.15°. The repeated error of the measurement system is less than 0.36 mm, which can meet the requirements of the 3D shape measurement of the complex workpiece.
Gastric cancer with liver metastasis is defined as advanced gastric cancer and remains one of the deadliest diseases with poor prognosis. Approximately 4-14% of patients with gastric cancers ...presented with liver metastases at the initial diagnosis. Owing to its incurability, first-line treatment for gastric cancer with liver metastases is systematic chemotherapy, whereas surgery is usually performed to alleviate severe gastrointestinal symptoms. However, continuously emerging retrospective studies confirmed the role of surgery in gastric cancer with liver metastases and showed significantly improved survival rate in patients assigned to a group of surgery with or without chemotherapy. Therefore, more and more convincing data that resulted from prospective randomized clinical trials is in need to clarify the surgery strategies in patients with gastric cancer with liver metastasis.
: As a component of GINS complex, GINS4 is essential for initiating DNA replication and elongation of the cell cycle G1/S phase in eukaryotes and plays a vital role in normal physiological processes. ...However, the precise functions and regulation mechanisms of GINS4 in human tumors remain elusive.
: GINS4 expression was analyzed in gastric cancer tissues by qRT-PCR and western blotting, and its clinical relevance was studied using TMA. The biological functions of GINS4 were detected
and
. cDNA array, co-IP, GST pull-down and GTPase activation assays were performed to investigate the downstream regulation mechanism of GINS4. Upstream regulation mechanism of GINS4 was explored and demonstrated by circRNA sequencing, bioinformatics analysis, luciferase reporter assay and rescue experiments.
: Strikingly high GINS4 expression was detected in gastric cancer tissues and correlated with poor differentiation, advanced tumor stage, invasion depth and lymph node metastasis. GINS4 promoted cell growth and metastasis
and
, and suppressed cell apoptosis
. Mechanistically, GINS4 activated Rac1/CDC42 through directly binding to Rac1/CDC42, thereby activating their downstream pathways. Furthermore, circMLLT10 acts as a miR-509-3-5p sponge to attenuate its repressive effect on target GINS4. In addition, circMLLT10 promoted cell growth and metastasis and suppressed cell apoptosis, whereas miR-509-3-5p inhibited cell growth and metastasis and promoted cell apoptosis.
: The findings indicate for the first time that the novel GINS4 axis promotes gastric cancer cell growth and progression by activating Rac1 and CDC42. GINS4 may be a promising biomarker and target for diagnosis and treatment of gastric cancer.
Abstract
Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ...ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m
6
A modification on
FDX1
mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore– elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.
Background
Podocalyxin-like 1 (PODXL) was reported to be closely associated with the development of various cancers, yet its functional roles and molecular mechanisms remain vague. The aim of our ...study was to investigate the clinical significance, biological function and molecular mechanism of PODXL in gastric cancer (GC).
Methods
The level of PODXL in GC tissues was detected applying GC tissues microarray, fresh GC tissues and public database (Oncomine). The invasion, metastasis and tumorigenesis role of PODXL were performed in vitro and in vivo. The correlations between KLF4 and PODXL was determined in GC tissues microarray and fresh GC tissues, and the molecular regulatory mechanism between KLF4 and PODXL was explored in vitro.
Results
The high level of PODXL was detected in GC tissues with advanced T stage, lymph node metastasis, Union for International Cancer Control stage and poor differentiation. And Cox proportional hazards model revealed that PODXL can serve as an independent prognostic indicator for disease-free survival and overall survival of GC patients. Moreover, downregulation of PODXL could inhibit EMT and reduce invasion and metastasis in vitro as well as tumorigenesis in vivo. Additionally, our findings showed that PODXL may be a significant downstream target of KLF4.
Conclusions
KLF4/PODXL signaling pathway assumes an irreplaceable role in tumorigenesis, invasion and metastasis of human GC and PODXL serves as an independent prognostic indicator for GC patients.
GINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G1/S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain ...unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease‐free survival of CRC patients. Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel‐like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC.
Our research shows that Krüppel‐like factor 4/GINS complex subunit 4 (GINS4) signaling pathway could play important role in tumorigenesis and growth of human colorectal cancer (CRC). GINS4 could be an important predictor indicator for the prognosis of CRC patients.
The impact localization is a typical inverse problem to identify the damage source of structures. To overcome the positioning problems of the low resolution caused by sparse reference points, a ...weighted spectral cross-correlation (WSCC) method is proposed. First, a mathematical model with a series of Fiber Bragg Grating (FBG) sensors is built to generate a database of transient frequency responses of each reference point when random shock happens. Second, to identify the spectrum difference between the impact point and the reference point, a cross correlation model is built by mean and normalization operations on the frequency domain. Third, to figure out the impact point among the adjacent reference points, bicubic spline interpolation is realized by subdividing the grid of the WSCC. To validate the accuracy of our suggested method, an impact localization system is designed with a multi FBG sensor network and a composite laminate. The experimental result shows that the error of our suggested method is almost ten times lower than that of other traditional methods. The weighted spectral cross-correlation has advantages in the field of structural health monitoring.
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