Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Quasi-Chromophores Segregated by Single-Chain Nanoparticles of Fluorinated Zwitterionic Random Copolymers Showing Remarkably Enhanced Fluorescence Emission Capable of Fluorescent Cell Imaging.

Organic and polymer fluorescent nanomaterials are a frontier research focus. Here in this work, a series of fluorinated zwitterionic random copolymers end-attached with a quasi-chromophoric group of pyrene or tetraphenylethylene (TPE) are well synthesized via atom transfer radical polymerization with activators regenerated by electron transfer (ARGET ATRP). Those random copolymers with total degree of polymerization 100 or 200 are able to produce fluorescent single-chain nanoparticles (SCNPs) through intra-chain self-folding assembly with quite uniform diameters in the range of 10-20 nm as characterized by dynamic light scattering and transmission electron microscopy. By virtue of the segregation or confinement effect, both SCNPs functionalized with pyrene or TPE group are capable of emitting fluorescence, with pyrene tethered SCNPs exhibiting stronger fluorescence emission reaching the highest quantum yield ≈20%. Moreover, such kind of fluorescent SCNPs manifest low cytotoxicity and good cell imaging performance for Hela cells. The creation of fluorescent SCNPs through covalently attached one quasi-chromophore to the end of one fluorinated zwitterionic random copolymer provides an alternative strategy for preparing polymeric luminescence nanomaterials, promisingly serving as a new type of fluorescent nanoprobes for biological imaging applications.

Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway

Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7. ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein–Barr virus (EBV) status might be indicative to the use of ICIs. In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies (AU)

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression.

BACKGROUND: Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations. However, preliminary studies have documented the pathophysiological changes in certain brain regions, such as the cerebellum, highlighting a need for further research to support the current understanding of this disease. AIM: To study brain changes in depressed adolescents. METHODS: This study enrolled 34 adolescents with depression and 34 age-, sex-, and education-level-matched healthy control (HC) individuals. Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow (CBF) analysis, respectively. Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses. RESULTS: The cerebellum, superior frontal gyrus, cingulate gyrus, pallidum, middle frontal gyrus, angular gyrus, thalamus, precentral gyrus, inferior temporal gyrus, superior temporal gyrus, inferior frontal gyrus, and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals. These patients with depression further presented with a pronounced drop in CBF in the left pallidum (group = 98, and peak t = - 4.4324), together with increased CBF in the right percental gyrus (PerCG) (group = 90, and peak t = 4.5382). In addition, 17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus (r = - 0.5231, P < 0.01). CONCLUSION: The right PerCG showed structural and CBF changes, indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway.

Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7. ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein-Barr virus (EBV) status might be indicative to the use of ICIs. In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies.

Facile Synthesis of Liquid Crystal Dimers Bridged with a Phosphonic Group.

Liquid crystal (LC) dimers with well-defined composition and structure arouse broad attentions for their exhibiting LC properties beyond conventional low molar mass mesogens and serving as fascinating model compounds for LC polymers. Here in this work, a series of LC dimers bridged with a phosphonic group have been synthesized through a facile free radical mediated addition reaction between hypophosphorous acid and vinyl terminated cyanobiphenyl mesogens with variant length alkyl spacers. In addition, two esterified derivatives and a group of mono-addition homologues with a terminal phosphonic acid group have also been prepared for comparison study. All the newly synthesized compounds exhibit monotropic nematic (N) phase with typical schlieren textures except for the LC dimer with the longest eleven-methylene spacer, which surprisingly shows twist-bend nematic (NTB ) phase directly from the isotropic state upon cooling. Moreover, the thermal transition properties such as the nematic-isotropic transition temperatures and associated entropy changes of the series LC dimers display a modest odd-even effect. Furthermore, both the LC dimers and the mono-addition homologues in N phase are quite easy to achieve homeotropic alignment upon annealing thanks to the supramolecular interactions between the introduced phosphonic acid group and the hydroxylated glass surface. This work thus provides a novel synthesis strategy for a class of LC materials bridged with a phosphonic acid group prone to further functionalization, which may serve as promising vertical alignment agents and pave the way for developing a new kind of functionalized LC materials of NTB phase.

Up-frameshift Protein 1 Promotes Tumor Progression by Regulating Apoptosis and Epithelial-Mesenchymal Transition of Colorectal Cancer.

Background: Recently, accumulating evidence confirmed that up-frameshift protein 1 (UPF1) was aberrantly expressed in various cancers. However, the molecular mechanism mediated by UPF1 underlying colorectal carcinogenesis remains unclear. Method: Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction analysis were used to determine the expression level of UPF1 in colorectal cancer (CRC) tissues. CCK-8, EdU, transwell assay, and flow cytometry were performed to investigate the biological significance of UPF1. Epithelial-mesenchymal transition (EMT) and apoptosis associated markers were detected by western blotting. Results: We found that UPF1 expression was upregulated in CRC tissues and cell lines. Clinical analysis revealed that high UPF1 expression was positively correlated with advanced stage, lymph node metastasis and shorter survival. Knockdown of UPF1 suppressed cell proliferation and cell cycle progression. Functionally, UPF1 promotes tumor metastasis by inducing epithelial to mesenchymal transition. Further investigations revealed that knockdown of UPF1 promoted apoptosis through triggering DNA damage. Conclusions: Taken together, this research revealed that UPF1 plays an oncogenic role in CRC via regulating EMT and apoptosis and may be a potential therapeutic target for CRC.

Identification and Validation of EMT-Related lncRNA Prognostic Signature for Colorectal Cancer.

Background: This study aimed to explore the biological functions and prognostic role of Epithelial-mesenchymal transition (Epithelial-mesenchymal transition)-related lncRNAs in colorectal cancer (CRC). Methods: The Cancer Genome Atlas database was applied to retrieve gene expression data and clinical information. An EMT-related lncRNA risk signature was constructed relying on univariate Cox regression, Least Absolute Shrinkage and Selector Operation (LASSO) and multivariate Cox regression analysis of the EMT-related lncRNA expression data and clinical information. Then, an individualized prognostic prediction model based on the nomogram was developed and the predictive accuracy and discriminative ability of the nomogram were determined by the receiver operating characteristic curve and calibration curve. Finally, a series of analyses, such as functional analysis and unsupervised cluster analysis, were conducted to explore the influence of independent lncRNAs on CRC. Results: A total of 581 patients were enrolled and an eleven-EMT-related lncRNA risk signature was identified relying on the comprehensive analysis of the EMT-related lncRNA expression data and clinical information in the training cohort. Then, risk scores were calculated to divide patients into high and low-risk groups, and the Kaplan-Meier curve analysis showed that low-risk patients tended to have better overall survival (OS). Multivariate Cox regression analysis indicated that the EMT-related lncRNA signature was significantly associated with prognosis. The results were subsequently confirmed in the validation dataset. Then, we constructed and validated a predictive nomogram for overall survival based on the clinical factors and risk signature. Functional characterization confirmed this signature could predict immune-related phenotype and was associated with immune cell infiltration (i.e., macrophages M0, M1, Tregs, CD4 memory resting cells, and neutrophils), tumor mutation burden (TMB). Conclusions: Our study highlighted the value of the 11-EMT-lncRNA signature as a predictor of prognosis and immunotherapeutic response in CRC.

UHRF1 Could Be a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Hepatocellular Carcinoma.

OBJECTIVE: This study was performed to investigate the relationship among UHRF1 expression, its biological function and immune infiltration in human hepatocellular carcinoma (HCC). METHODS: Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, and The Cancer Genome Atlas (TCGA) databases were used to analyze UHRF1 expression between HCC and normal tissues. Subsequently, GEPIA, TCGA-Portal, Kaplan-Meier Plotter, Protein Atlas and SurvExpress databases were utilized for survival analysis. UHRF1 co-expression genes were identified via the cBioPortal and LinkedOmics databases. Further, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. Protein-protein interaction (PPI) networks was constructed by STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm were employed to assess the correlation between UHRF1 and tumor immune infiltrates on TCGA database. TIMER 2.0 database was used to explore the correlation of UHRF1 expression and immune infiltration level in HCC. Additionally, RT-qPCR was used to analyze the expression of UHRF1 and the relative genes in HCC cell lines. RESULTS: Expression level of UHRF1 was upregulated in HCC tissues compared with paired normal tissues (P < 0.05 in GEPIA; P = 1.78E-6 in Oncomine; and P < 0.0001 in TCGA). Its high expression was significantly related with a shorter overall survival in five databases (P < 0.05). Function enrichment analysis demonstrated that functions of UHRF1 concentrated in cell division process and cell cycle (P < 0.05). High UHRF1 expression exhibited dysregulated immune infiltration (ie, neutrophils, eosinophils, dendritic cells resting, macrophages M2, macrophages M0) and poor survival of high UHRF1 expression was tight correlated with immune infiltration status. Moreover, TP53 mutation can lead to high expression of UHRF1 (P = 4.2E-10). CONCLUSION: UHRF1 might function as an oncogene via inducing dysregulated immune infiltration in HCC and was identified as a novel prognostic biomarker and potential therapeutic target for HCC.

Standardization of Raman spectra using variable penalty dynamic time warping.

Raman spectroscopy can provide structural fingerprints to identify molecules by means of spectral library searching. However, it is difficult to share the spectral library between different Raman spectrometers because of the nonlinear displacement in Raman shift. In this study, we propose a Raman spectra Standardization method using Variable Penalty dynamic time warping (RS-VPdtw), which can synchronize the nonlinear displacement between spectra acquired with different spectrometers. We have compared the standardization performance of RS-VPdtw and MWFFT on the spectra of 13 real samples acquired with 6 different spectrometers. The mean spectral similarity of RS-VPdtw and MWFFT increased from 0.79 to 0.97 and 0.91 respectively. Results show that RS-VPdtw is significantly better than MWFFT in Raman spectra standardization. The Raman spectra acquired with different spectrometers can be standardized by RS-VPdtw to search the same spectral library, which can avoid the time-consuming and labor-intensive reestablishment of spectral libraries for different spectrometers. This means that RS-VPdtw is a promising and valuable method to solve the spectra standardization problem in large-scale applications of Raman spectroscopy.

UPF1: a potential biomarker in human cancers.

Recently, Up-frameshift protein 1 (UPF1) is reported to be downregulated in various cancers and its low expression is closely correlated with poor prognosis. UPF1 is well known as a master regulator of nonsense-mediated mRNA decay (NMD), which serves as a highly conserved mRNA surveillance process protecting cells from aberrant toxic transcripts. Due to dysfunction of UPF1, NMD fails to proceed, which contributes to tumor initiation and progression. This review shows a brief summary of the aberrant expression, functional roles and molecular mechanisms of UPF1 during tumorigenesis. Increasing evidence has indicated that UPF1 could serve as a potential biomarker for cancer diagnosis and treatment for future clinical applications in cancer.

Spatial distribution of rural population using mixed geographically weighted regression: Evidence from Jiangxi Province in China.

On the basis of the spatial panel data of 2000, 2005, 2010, and 2015, this study uses a mixed geographically weighted regression model to explore the spatial distribution characteristics and influencing factors of the rural (permanent) population in Jiangxi Province, China. Results show that residents in the county area have a significant spatial positive autocorrelation, especially in the lake and mountain areas and the global Moran' I index is more than 0.05. The influence of social and economic factors presents spatial homogeneity. The effect of urbanization and per capita disposable income is negative, whereas that of agricultural output value and rural electricity consumption is positive. The influence of climate factors presents spatial heterogeneity. The influence coefficient of rainfall in 2015 ranges from [-0.061, 0.133], which has a negative effect on the southwest mountain areas and a positive effect on the northeast lake areas., The influence coefficient of temperature in 2015 ranges from [-0.110, 0.094], which has a positive effect on the southwest mountain areas and a negative effect on the northeast lake areas. The influence coefficients of wind speed and relative humidity range from [-0.090, 0.153] and [-0.069, 0.130] in 2015 respectively, which further reinforce this effect. Therefore, scholars should pay attention to the universal adaptability of economic and social factors. Moreover, they should consider the spatial difference of climatic factors to promote urbanization following the local conditions. Finally, policymakers and concerned non-governmental institutions should fully understand the sensitivity of the rural population in underdeveloped mountain areas to climate factors to promote their rational distribution.

AVL9 is Upregulated in and Could Be a Predictive Biomarker for Colorectal Cancer.

PURPOSE: This study aimed to explore the function and clinical significance of AVL9 in colorectal cancer (CRC). MATERIALS AND METHODS: The GEO, TCGA, and GEPIA databases were searched to evaluate the expression level of AVL9, while the SurvExpress online tool was used to explore its related clinical survival prognosis. The cBioPortal and LinkedOmics databases were used to identify AVL9 expression-related genes. Protein-protein interaction (PPI) networks were analyzed using Cytoscape 3.7.1 and DAVID6.8, which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment. The immunohistochemistry of AVL9 in CRC was detected using an online tool protein atlas. RNA isolation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to detect AVL9 expression in tissue and plasma samples. RESULTS: Our study confirmed that AVL9 was highly expressed in CRC lesions versus the adjacent normal tissues (P < 0.001). High AVL9 expression was negatively associated with survival outcomes (P < 0.05). GO analysis showed that AVL9 expression-related genes were enriched in single organismal cell-cell adhesion, post-transcriptional regulation of gene expression, and negative regulation of the vascular endothelial growth factor receptor signaling pathway (P < 0.05). On a KEGG pathway analysis, these genes were mainly involved in progesterone-mediated oocyte maturation, axon guidance, the insulin signaling pathway, and the ubiquitin-mediated proteolysis signaling pathways (P < 0.05). In the PPI analysis, the KBTBD2, KIAA1147, EPDR1, and RNF216 genes interacted with AVL9, and GEPIA predicted that their expression levels were all positively correlated with AVL9. Furthermore, a clinicopathological parameter analysis found that high AVL9 expression was positively correlated with differentiation and TNM stage. RT-qPCR analysis further showed that plasma AVL9 expression was upregulated in CRC patients versus healthy controls. CONCLUSION: AVL9 could serve as a potential biomarker and therapeutic target for CRC.

Spatial distribution of rural population from a climate perspective: Evidence from Jiangxi Province in China.

The research on rural population distribution from a climate perspective is rare. Therefore, this study adopts this perspective and uses the ordinary least squares and spatial econometric models to explore the spatial distribution characteristics of the rural population in the Poyang Lake ecological economic zone. Results show that (1) a significant spatial autocorrelation is present in the distribution of rural population, and a spatial correlation exists between the population distribution and climatic factors, (2) the influence of climatic factors on the distribution of rural population in the Poyang Lake ecological economic zone is greater than that of economic factors, and (3) the annual average sunshine and annual average rainfall have a significant negative effect on the distribution of the regional rural population, which is contrary to the expectations., so we then analyze this negative effect on the regional rural population distribution. It is found that (1) the influence of climate factors on the distribution of rural population in lake area is far more than that of economic factors, and more consideration should be given to the influence of climate factors on the population distribution in the lake area, (2) different geographical capital and natural resource endowment, the influence of climate on micro-regional population distribution may be different from the general law, (3) the spatial measurement model which takes spatial dependence into account can reveal the influence of climate on rural population distribution more accurately.

CircRNA_100876 Is Upregulated in Gastric Cancer (GC) and Promotes the GC Cells' Growth, Migration and Invasion via miR-665/YAP1 Signaling.

The present study aimed to investigate the biological function and relative mechanisms of circRNA_100876 in gastric cancer (GC). To this end, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine the expression of circRNA_100876 and miR-665 in GC tissues and cells, and circRNA_100876 expression was depleted by the transfection of circ_100876-targeting siRNAs. CCK-8, flow cytometry, and Transwell assays were applied to examine GC cell cycle distribution, proliferation, apoptosis, migration, and invasion abilities. Proteins related to apoptosis and epithelial-mesenchymal transition (EMT) were detected by western blotting. Luciferase reporter assays were conducted to verify the direct target site between circRNA_100876 and miR-665. Our study confirmed that circRNA_100876 was highly expressed in GC lesions compared with the adjacent normal tissues (P < 0.001). High circRNA_100876 expression was negatively associated with survival outcome (P = 0.000). Furthermore, the down-regulation of circRNA_100876 could inhibit GC cell proliferation, invasion, and migration by suppressing the EMT pathway. Further study suggested that circRNA_100876 could act as a competing endogenous RNA by sequestering miR-665, and luciferase activity assay indicated that circRNA_100876 could bind directly with miR-665. Moreover, we found that Yes-associated protein 1 (YAP1) was the downstream target gene of miR-665, miR-665 knockdown could up-regulate YAP1 expression in MKN45 cells, and YAP1 knockdown could inhibit MKN45 cell proliferation, migration and invasion. Therefore, we demonstrated that circRNA_100876 over-expression in GC could promote GC tumor growth, migration and invasion and exert its effects through miR-665/YAP1 signaling.

How to achieve auto-identification in Raman analysis by spectral feature extraction & Adaptive Hypergraph.

With the miniaturization of Raman spectrometers, Raman spectroscopy (including Surface-enhanced Raman spectroscopy) has been widely applied to various fields, especially towards rapid detection applications. In order to deal with the accompanied massive databases, large numbers of Raman spectra require to be handled and identified in an effective and automatic manner. This paper proposes an algorithm of material auto-identification, which makes use of machine learning methods to analyze Raman spectra. Firstly, a universal method of spectral feature extraction is designed to automatically process Raman spectra after the background subtraction. Secondly, the extracted feature vectors are used to classify and identify target materials by Adaptive Hypergraph (AH), an efficient classifier in the field of machine learning, in a manner of automation with an accuracy rate of ~99%. Compared with Support Vector Machine (SVM) and Random Forest (RF), two typical methods of classification, the AH classifier provides better performance free of tuning any parameter facing different targets. Thirdly, Cubic Spline Interpolation is introduced to enhance the universal of the proposed algorithm between different databases from different Raman spectrometers with variant vendors. The identification accuracy rate is up to 98% using the high frequency sampling spectra as the learning and the low frequency sampling ones as the testing, respectively.

Improved sensitivity and reproducibility in electrochemical detection of trace mercury (II) by bromide ion & electrochemical oxidation.

Nanostructured gold electrodes have been widely used for electrochemical trace analysis of Hg2+ because Hg2+ has superior specificity for the formation of gold amalgam. However, it is still very challenging to achieve both high sensitivity and reproducibility, especially for real environmental water samples due to surface poisoning by organic residues. In this work, we developed two strategies for addressing these challenges. First, we added NaBr (with a final concentration of 0.01 M) to the analytes; this enhanced the sensitivity by two orders of magnitude and improved the reproducibility to be better than RSD <15% because of the synergetic interaction of Br- with Hg2+ and gold at the interface. Second, we developed a pre-oxidation method using a glassy carbon electrode to remove organic residue from the analyte before Hg2+ analysis. The combination of these two approaches results in an efficient, reliable, and fast electrochemical detection technique for on-site trace analysis of Hg2+ that is in concentrations lower than that required by WHO for drinking water.

CircRNA_104916 regulates migration, apoptosis and epithelial-mesenchymal transition in colon cancer cells.

Circular RNAs (circRNAs) are a class of noncoding RNAs that are differentially expressed in tissues with a great potential in regulating the tumorigenesis and metastasis. The COX proportional hazard model predicts that among these, the relative expression of circRNA_104916 and lymphatic metastatic status independently predict the prognosis of patients with cancer. In the present study, we show that circRNA_104916 is downregulated in colorectal cancers as compared to the adjacent normal tissues. The expression of circRNA_104916 is negatively correlated with the tumor size, T stage and lymphatic metastasis. Patients with higher relative circRNA_104916 expression have a better post-operative disease-free survival as compared with those with lower relative expression. Forced expression of circRNA_104916 induces cell apoptosis and G2/M phase arrest by activating apoptosis pathway and cyclin proteins, thereby inhibiting proliferation of colon cancer cell lines, including LoVo and Caco-2. Additionally, overexpression of circRNA_104916 significantly suppresses migration and invasion of tumor cells by inhibiting the epithelial-mesenchymal transition. In conclusion, this study reveals that circRNA_104916 is a potential biomarker and therapeutic target for colorectal cancers.

Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer.

BACKGROUND: Recently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662 in the regulation of CRC progression. METHODS: Both gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets were used to evaluate the expression of linc00662. RT-qPCR was used to analyze the expression of linc00662, miR-497-5p, and AVL9 in CRC clinical samples and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assay, and xenograft model were used to investigate the effect of linc00662 on CRC cell proliferation, cell cycle, and metastasis. Western blot analysis was used to analyze the expression of the epithelial-mesenchymal transition (EMT)-associated markers. Furthermore, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. Dual-luciferase reporter assays were used to analyze the regulatory relationships among linc00662, miR-497-5p, and AVL9. RESULTS: In this study, we found that the expression of linc00662 was significantly upregulated in CRC tissues compared to normal tissues and positively correlated with tissue differentiation, T stage, and lymphatic metastasis. Further, our data showed that the expression of linc00662 was positively associated with lymph node metastasis, TMN stage, and poor-moderate differentiation. Patients with higher linc00662 expression level were more likely to have poorer overall survival. Knockdown of linc00662 inhibited CRC cell growth, induced cell apoptosis, triggered cell cycle arrest at G2/M phase, and suppressed cell migration and invasion through regulating the EMT pathway. Further, mechanistic studies revealed that knockdown of linc00662 significantly reduced the expression of AVL9, a direct target of miR-497-5p. CONCLUSIONS: Linc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy.