MicroRNA-409-3p regulates cell invasion and metastasis by targeting ZEB1 in breast cancer.

MicroRNA-409-3p (miR-409-3p) is an miRNA expressed by embryonic stem cells, and our previous study demonstrated depressed miR-409-3p expression in human breast cancer (BC) cell lines; however, its role and function in BC metastasis are still unknown. The purpose of this study was to examine the expression levels of miR-409-3p in human BC and its role in the metastasis of BC. We analyzed the status of miR-409-3p expression in BC tissues by quantitative real-time polymerase chain reaction (PCR) and its relationship to the clinicopathologic features of patients with BC. To study the role of miR-409-3p in BC metastasis, the invasion ability of BC cells was detected by transwell invasion assays and wound healing assays. WST-1 assays and colony formation assays were used to investigate cell proliferation. Luciferase reporter assays were used to verify that miR-409-3p targeted zinc-finger E-box-binding homeobox 1 (ZEB1). Western blot analyses and transwell assays were carried out to assess ZEB1 expression and its role in BC cell metastasis. The expression of miR-409-3p was lower in tumor tissues than in noncancerous breast tissues. We verified that miR-409-3p levels were downregulated and significantly correlated with poor outcomes in patients with BC. Overexpression of miR-409-3p inhibited cellular proliferation and suppressed cellular migration and invasion in vitro and in vivo. Dual-luciferase reporter assays showed that miR-409-3p binds the 3'-untranslated region (3'-UTR) of ZEB1, suggesting that ZEB1 is a direct target of miR-409-3p. Western blot analysis confirmed that overexpression of miR-409-3p reduced ZEB1 protein levels. These data demonstrate that miR-409-3p plays an important role in regulating the metastasis of BC, which is involved in the post-transcriptional repression of ZEB1. Our results indicate that miR-409-3p can regulate the invasion and metastasis process of BC by targeting ZEB1 and may serve as a new prognostic marker and therapeutic target for treating BC metastasis. © 2016 IUBMB Life, 68(5):394-402, 2016.

Clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization on hepatocellular carcinoma.

BACKGROUND: The aim of this study was to evaluate the clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). METHODS: Data from 117 patients with HCC who underwent hepatectomy between December 2010 and February 2014 were retrospectively reviewed. In total, 55 patients underwent surgical resection only (group A), and 62 patients underwent surgical resection with adjuvant TACE (group B). The perioperative clinical indicators, postoperative sequential treatment, and follow-up were compared between the two groups of patients. The Kaplan-Meier method was used to compare survival between the groups, and prognostic factors were evaluated by a Cox proportional hazard model. RESULTS: The two groups showed no significant difference in age, gender, preoperative A-fetoprotein (AFP) values, preoperative Child-Pugh score, hepatitis B virus(HBV) DNA levels, duration of surgery, hepatectomy technique, albumin values 1-week postoperative, postoperative complications, duration of postoperative hospital stay, cirrhosis, tumor size, tumor differentiation, tumor encapsulation, satellite nodules, or microvascular infiltration. Cox regression analysis revealed that tumor size, satellite nodules, and microvascular infiltration were significantly independent prognostic factors (P = 0.001, 0.002, and 0.001). Of the 117 patients, the 1-, 2-, and 3-year disease-free survival rates were 64.5, 50.0, and 41.9%, respectively, for group B (62 patients) and 45.5, 36.4, and 30.9%, respectively, for group A (55 patients). Although improving trends of disease-free survival were observed in the adjuvant TACE group, there was a significant difference in postoperative 1-year survival between the two groups (P = 0.04) but no significant difference in postoperative 2- and 3-year survival. In patients with tumor size >5 cm, the 1-, 2-, and 3-year disease-free survival rates were 41.7, 25.0, and 12.5%, respectively, for group B and 11.8, 0, and 0%, respectively, for group A. There was a significant difference in postoperative 1- and 2-year survival between the two groups (P = 0.04 and 0.03, respectively) but no significant difference in postoperative 3-year survival. In patients with microvascular infiltration, the 1-, 2-, and 3-year disease-free survival rates were 42.3, 26.9, and 15.4%, respectively, for group B and 12.5, 4.2, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.02, 0.03, and 0.045, respectively). In patients with satellite nodules, the 1-, 2-, and 3-year disease-free survival rates were 50.0, 50, and 40%, respectively, for group B and 17.6, 0, and 0%, respectively, for group A. There was a significant difference between the two groups (P = 0.04, 0.01, and 0.03, respectively). In patients with tumor size ≤5 cm, without satellite nodules, or without microvascular infiltration, there was no significant difference between the two groups in the 1-, 2-, or 3-year disease-free survival rates. Of 117 patients overall, 18 (15.4%) developed hepatitis B virus reactivation: 2 (3.6%) patients in group A and 16 (25.8%) patients in group B. There was a significant difference between the two groups (P = 0.000). Of these patients, one (1.8 %) patient in group A and five (8.1 %) patients in group B developed hepatitis due to hepatitis B virus reactivation. There was a significant difference between the two groups (P = 0.000). CONCLUSIONS: Postoperative adjuvant TACE can improve the 1-year disease-free survival rate of HCC patients. Postoperative adjuvant TACE may improve 2- and 3-year disease-free survival rates, but no statistical significance was found. For patients with tumor size >5 cm, postoperative adjuvant TACE can improve 1- and 2-year disease-free survival rates, and postoperative adjuvant TACE may improve the 3-year disease-free survival rate. For HCC patients with tumor size ≤5 cm, postoperative adjuvant TACE may improve the 1-, 2-, and 3-year disease-free survival rates, but no statistical significance was found. For patients with microvascular infiltration or satellite nodules, postoperative adjuvant TACE can improve the 1-, 2-, and 3-year disease-free survival rates. For patients without microvascular infiltration or without satellite nodules, postoperative adjuvant TACE cannot improve 1-, 2-, or 3-year disease-free survival rates. For patients with tumor size >5 cm with microvascular infiltration or with satellite nodules, postoperative adjuvant TACE was suggested. Hepatitis B virus reactivation can occur in patients with postoperative adjuvant TACE; thus, antiviral treatment was suggested for these patients.

Increased cancer risk associated with the -607C/A polymorphism in interleukin-18 gene promoter: an updated meta-analysis including 12,502 subjects.

PURPOSE: Increasing investigations have been performed on the association of -607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and have yielded conflicting results. To derive a more precise estimation of the association, we performed an updated meta-analysis of all eligible studies. METHODS: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) were pooled by the fixed-effects/random-effects model in STATA 12.0 software. RESULTS: This meta-analysis included 29 studies with 6,026 cases and 6,476 controls. Overall, significantly increased cancer risk was observed (A vs C: OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI: 1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25, Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31, Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results suggested a significantly increased risk of cancer in Asian population (CA vs CC: OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI: 1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95% CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64, Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA; AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no significant association was found in Caucasian or African populations. In the subgroup analysis by cancer type we found a significantly increased susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00-1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02-3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00-1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI: 1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75, Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70, Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09-1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI: 1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66, Pheterogeneity=0.700). CONCLUSIONS: The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations. More studies with diverse ethnic groups, larger sample size, and well controlled confounding factors are warranted to further investigate the association.

Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway.

The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis.

Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.

Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.

Response of Propsilocerus akamusi (Diptera: Chironomidae) to the leachates from AMD-contaminated sediments: Implications for metal bioremediation of AMD-polluted areas.

Acid mine water (AMD) is a global environmental problem caused by coal mining with the characteristics of low pH and high concentrations of metals and sulfates. It is a pertinent topic to seek both economical and environmentally friendly approaches to minimize the harmful effects of AMD on the environment. Insect larvae are considered a promising solution for pollution treatment. Chironomidae is the most tolerant family to contaminants in pools and its larvae have a strong capacity for metal accumulation from sediment. This paper aimed to evaluate the larvae of Propsilocerus akamusi, a dominant species in the chironomid community, as a new species for entomoremediation in AMD-polluted areas. We detected the toxic effects of AMD on P. akamusi larvae based on their survival and the trace metals bioaccumulation capabilities of P. akamusi larvae. Moreover, we analyzed the expression patterns of four stress-response genes, HSP70, Eno1, HbV, and Hb VII in P. akamusi larvae. Our results revealed that AMD exposure did not significantly affect the survival of the P. akamusi larvae and individuals exposed to some AMD gradients even exhibited higher survival. We also observed the significantly accumulated concentrations of Fe, Ni, and Zn as well as higher bioaccumulation factors (BAFs) for Ni and Zn in the P. akamusi larvae exposure to AMD. Induced expression of Eno1 and Hb VII may play important roles in the AMD tolerance of P. akamusi larvae. This study indicated the potential application of P. akamusi larvae in the metal bioremediation of AMD-polluted areas. STATEMENT OF ENVIRONMENTAL IMPLICATION: Acid mine drainage (AMD) is a global environmental problem related to coal mining activities. AMD pollution has become a long-term, worldwide issue for its interactive and complex stress factors. Bioremediation is an effective method to remove the metals of AMD from wastewater to prevent downstream pollution. However, the disadvantages of the slow growth rate, susceptibility to seasonal changes, difficult post-harvest management, and small biomass of hyperaccumulating plants greatly limit the usefulness of phytoremediation. Insect larvae may be useful candidate organisms to overcome these shortcomings and have been considered a promising pollution solution. Propsilocerus akamusi is a dominant species in the chironomid community and is distributed widely in many lakes of eastern Asia. This species has extraordinary abilities to resist various stresses. This research is the first time to our knowledge to evaluate the application of P. akamusi as a new species in entomoremediation in AMD-contaminated areas.

Accurate and fast localization of EBSD pattern centers for screen moving technology.

The authors of this study develop an accurate and fast method for the localization of the pattern centers (PCs) in the electron backscatter diffraction (EBSD) technique by using the model of deformation of screen moving technology. The proposed algorithm is divided into two steps: (a) Approximation: We use collinear feature points to obtain the initial value of the coordinates of the PC and the zoom factor. (b) Subdivision: We then construct a deformation function containing the three parameters to be solved, select a large region for global registration, use the inverse compositional Gauss-Newton (ICGN) to optimize the objective function, and obtain the results of iteration of the PC and the zoom factor. The proposed algorithm was applied to simulated patterns, and yielded an accuracy of measurement of the PCs that was better than 4.6×10-6 of their resolution while taking only 0.2 s for computations. Moreover, the proposed algorithm has a large radius of convergence that makes it robust to the initial estimate. We also discuss the influence of factors of mechanical instability on its results of calibration during the insertion of the detector, and show that errors in measurements caused by the tilt motion of the camera are related only to the tilt angle of its motion and the detector distance, and are unrelated to the distance moved by it.

Increased expression of GPX4 promotes the tumorigenesis of thyroid cancer by inhibiting ferroptosis and predicts poor clinical outcomes.

BACKGROUND: Ferroptosis plays a critical role in suppressing cancer progression, and its essential regulator is glutathione peroxidase 4 (GPX4). High GPX4 expression can inhibit accumulation of iron, thus suppressing ferroptosis. However, its function in thyroid cancer has not been fully illuminated. Here, we explore the effect of GPX4 on thyroid cancer tumorigenesis and prognosis. METHODS: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, GPX4 expression was investigated in cancer tissues and adjacent tissues. We determined the biological functions of GPX4-associated differentially expressed genes (DEGs) by using the "clusterProfiler" R package. In addition, the predictive value of GPX4 in thyroid cancer was assessed by using Cox regression analysis and nomograms. Finally, we conducted several in vitro experiments to determine the influence of GPX4 expression on proliferation and ferroptosis in thyroid cancer cells. RESULTS: GPX4 expression was obviously elevated in thyroid cancer tissues compared with normal tissues. Biological function analysis indicated enrichment in muscle contraction, contractile fiber, metal ion transmembrane transporter activity, and complement and coagulation cascades. GPX4 overexpression was associated with stage T3-T4 and pathologic stage III-IV in thyroid cancer patients. Cox regression analysis indicated that GPX4 may be a risk factor for the overall survival of thyroid cancer patients. In vitro research showed that knockdown of GPX4 suppressed proliferation and induced ferroptosis in thyroid cancer cells. CONCLUSIONS: GPX4 overexpression in thyroid cancer might play an essential role in tumorigenesis and may have prognostic value for thyroid cancer patients.

Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression.

Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway.

Measurement of the pattern shifts for HR-EBSD with larger lattice rotations.

High-resolution electron backscattering diffraction (HR-EBSD) was used to measure rotations and elastic strains by matching diffraction patterns based on cross-correlation. However, the subset-based phase correlation algorithm was unable to determine pattern shifts accurately when large rotations occurred. In this paper, a new matching algorithm was proposed to measure pattern shifts and recover the elastic strain and lattice rotation with finite deformation theory. The algorithm was implemented in two steps: (a) Integral pixel matching: The pixel-related information of the Kikuchi patterns was mapped to the original three-dimensional sphere to obtain the image projected in parallel by using the feature points as the pattern center through the transformation of its spatial coordinates. The correlation between the images projected in parallel before and after deformation was then obtained. The locations of the integral pixels were determined by the peaks of the surface of correlation obtained by traversing all pixels in the search area. (b) subpixel refinement: the locations of subpixels were obtained by FAGN with an appropriate shape function involving rotation and translation. The algorithm was applied to dynamic simulated test sets, and its results were compared with those of the first-pass cross-correlation and the second-pass cross-correlation method with remapping. The proposed method was more robust in the case of rotation and solved the problem that displacement vectors could not be accurately measured when a larger lattice rotation occurred. The mean errors of the measured displacement, rotation, and strain components were 0.02 pixel, 0.5×10-4rad, and 1×10-4, respectively. Compared with the second-pass cross-correlation method, the angle of rotation was more precisely extracted.

Within-day variation and health risk assessment of trihalomethanes (THMs) in a chlorinated indoor swimming pool in China.

Trihalomethanes (THMs) are the most common species of disinfection by-products (DBPs) in swimming pools and have received widespread attention due to their risk to public health. However, studies examining within-day variation and the carcinogenic health risks from exposure to THMs in indoor swimming pools are limited. Our study aimed to detect the within-day variation of four THMs categories and carcinogenic health risk in indoor swimming pool water in Taiyuan, China, and to examine the correlations between THMs and environmental parameters. Our results showed chloroform (TCM) was the most abundant component in THMs with median concentrations from 0.038-0.118 µg/m3. TCM and THMs were significantly positively correlated with FCl and significantly negatively correlated with the cumulative number of swimmers (CNS) in the swimming pool. The concentration of total THMs and TCM, lifetime average daily doses (LADD) of TCM, and the total lifetime cancer risks (ELCR) values of THMs declined with time with the highest level occurring at 8:00 am. ELCR values of THMs were in the range of 1.368 × 10-5-1.968 × 10-5, which exceeded the negligible risk level (10-6) defined by US EPA. Our results suggest that THM occurrence and the carcinogenic health risks in pool water varied temporally. Exposure to pool water THMs may pose a carcinogenic risk to human health, especially at the pool's opening time.

Epidemiological Survey of First Human Brucellosis Outbreak Caused by the Sika Deer (Cervus nippon) - Guizhou Province, China, 2019.

What is already known on this topic? Brucellosis is a zoonotic infectious disease caused by Brucella spp. The main source of infection in human brucellosis is sick animals, mainly including sheep, goat, and cattle, but sika deer (Cervus nippon) can also cause human brucellosis. The first human brucellosis case in Guizhou Province was reported in 2009, and no brucellosis outbreak was reported caused by sika deer ever before. What is added by this report? This is the first reported outbreak of human brucellosis caused by sika deer in Guizhou Province. Inappropriate regulation of animal movement may be the main driver of introducing and spreading brucellosis in southern areas. The ability to diagnose brucellosis in both humans and animals was weak in the county where the outbreak took place. What are the implications for public health practice? It was suggested to prioritize occupational protection and health education for sika deer breeders. The inspection of the movement of animals and the reimbursement policy need to be improved.

Case Report and Systematic Review: Sarcomatoid Parathyroid Carcinoma-A Rare, Highly Malignant Subtype.

Background: Parathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This "confusing" cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC. Objective: To characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC. Materials and Methods: We collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison. Results: A 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4). Conclusion: SaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC-SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term.

Identification of Energy Metabolism Genes for the Prediction of Survival in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) samples were clustered into three energy metabolism-related molecular subtypes (C1, C2, and C3) with different prognosis using the gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). HCC energy metabolism-related molecular subtype analysis was conducted based on the 594 energy metabolism genes. Differential expression analysis yielded 576 differentially expressed genes (DEGs) among the three subtypes, which were closely related to HCC progression. Six genes were finally selected from the 576 DEGs through LASSO-Cox regression and used in constructing a six-gene signature-associated prognostic risk model, which was validated using the TCGA internal and three GEO external validation cohorts. The risk model showed that high ANLN, ENTPD2, TRIP13, PLAC8, and G6PD expression levels were associated with bad prognosis, and high expression of ADH1C was associated with a good prognosis. The validation results showed that our risk model had a high distinguishing ability of prognosis in HCC patients. The four enriched pathways of the risk model were obtained by gene set enrichment analysis (GSEA) and found to be associated with the tumorigenesis and development of HCC, including the cell cycle, Wnt signaling pathway, drug metabolism cytochrome P450, and primary bile acid biosynthesis. The risk score calculated from the established risk model in 204 samples and other clinical characteristics were used in building a nomogram with a good prognostic prediction ability (C-index = 0.746, 95% CI = 0.714-0.777). The area under the curves (AUCs) of the nomogram model in 1-, 2-, and 3-years were 0.82, 0.77, and 0.79, respectively. Then, qRT-PCR and immunohistochemistry were used to validate the mRNA expression levels of the six genes, and significant differences in mRNA and gene expression were observed among the tumor and adjacent tissues. Overall, our study divided HCC patients into three energy metabolism-related molecular subtypes with different prognosis. Then, a risk model with a good performance in prognostic prediction was built using the TCGA dataset. This model can be used as an independent prognostic evaluation index for HCC patients.

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway.

BACKGROUND: Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC). METHODS: The expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo. RESULTS: The invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway. CONCLUSIONS: These data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.

Activation of CXCL5-CXCR2 axis promotes proliferation and accelerates G1 to S phase transition of papillary thyroid carcinoma cells and activates JNK and p38 pathways.

C-X-C motif chemokine ligand 5 (CXCL5) is initially identified to recruit neutrophils by interacting with its receptor, C-X-C motif chemokine receptor 2 (CXCR2). Our prior work demonstrated that the expression levels of CXCL5 and CXCR2 were higher in the papillary thyroid carcinoma (PTC) tumors than that in the non-tumors. This study was performed to further investigate how this axis regulates the growth of PTC cells. B-CPAP cells (BRAFV600E) and TPC-1 cells (RET/PTC rearrangement) expressing CXCR-2 were used as in vitro cell models. Our results showed that the recombinant human CXCL5 (rhCXCL5) promoted the proliferation of PTC cells. rhCXCL5 accelerated the G1/S transition, upregulated the expression of a group of S (DNA synthesis) or M (mitosis)-promoting cyclins and cyclin-dependent kinases (CDKs), and downregulated CDK inhibitors in PTC cells. The CDS region of homo sapiens CXCL5 gene was inserted into an eukaryotic expression vector to mediate the overexpression of CXCL5 in PTC cells. The phosphorylation of c-Jun N-terminal kinases (JNK) and p38, and the nuclear translocation of c-Jun were enhanced by CXCL5 overexpression, whereas attenuated by CXCR2 antagonist SB225002. Additionally, CXCL5/CXCR2 axis, JNK and p38 pathway inhibitors, SB225002, SP600125 and SB203580, suppressed the growth of PTC cells overexpressing CXCL5 in nude mice, respectively. Collectively, our study demonstrates a growth-promoting effect of CXCL5-CXCR2 axis in PTC cells in vitro and in vivo.

Real-time out-of-plane displacement measurement using displacement compensation.

To determine out-of-plane displacement, it is challenging to simultaneously implement high resolution, wide range, and real-time measurement. This study proposes a method for displacement compensation based on the Michelson single-point displacement measurement system. The direction of fringe movement and amplitude of the object's displacement was calculated and converted into a feedback-tracking signal. The compensator was driven by the feedback signal to change the reference optical path to keep the fringes stable, and a method to detect fringe movement was developed. A convolutional neural network model was set to distinguish the direction of fringe movement, and a backpropagation neural network was used to calculate the amplitude of the movement using simple image processing at a high speed. The system's resolution was 10 nm in the range 210 µm, and the tracking time step was smaller than 200 ms. This provides an effective solution for high precision, real-time, and wide range measurement.

Correction to: LINC01296/miR-26a/GALNT3 axis contributes to colorectal cancer progression by regulating O-glycosylated MUC1 via PI3K/AKT pathway.

In the publication of this article [1], there is an error in Fig. 5G (panel 2, group of InmiR-26a + siSCR in HCT-8/5-FU, treated with 284.3 µM).

Correction: LncRNA HCP5A promotes follicular thyroid carcinoma progression via miRNAs sponge.

Following the publication of this article, the authors realized there was an error in Figure 3a wherein the migration panel of pcDNA3.3 was replicated in the invasion panel for HCP5. This error did not impact the conclusions of the article.

Correction to: LINC01296/miR-26a/GALNT3 axis contributes to colorectal cancer progression by regulating O-glycosylated MUC1 via PI3K/AKT pathway.

In the publication of this article [1], there is an error in Fig. 5C (panel 4, group of InmiR-26a + silinc01296 in SW620). The revised Fig. 5 which includes 5C has now been included in this correction.