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.

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.

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.

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.

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.

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.

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.

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).

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.

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

BACKGROUND: Long non-coding RNAs (LncRNAs) emerging as pivotal marker in the procession of cancer, including colorectal cancer (CRC). Abnormal O-glycosylation is a crucial modification during cancer malignancy. The aim of this work is to analyze the alteration of O-glycosylation involved in CRC progression. METHODS: qRT-PCR is utilized to screen the differential linc01296 expression in CRC tissues and cell lines. Functionally, CRC cell proliferation, aggressiveness and apoptosis are measured through relevant experiments, including CCK8 assay, colony formation assay, transwell assay, western blot and flow cytometry. Dual-luciferase reporter gene assay and RIP assay confirm the direct interaction between linc01296 and miR-26a. The xenografts and liver metatstatic nude mice models are established to show the inner effect of linc01296. RESULTS: Differential expression of linc01296 is confirmed and closely correlated with the malignancy of CRC cell lines and poor clinical prognosis. Moreover, alteration of linc01296 affects CRC cell proliferation, metastasis and chemoresistance to 5-fluorouracil (5-FU) in vitro. Mechanically, linc01296 acts as a direct target of miR-26a, and thereby influenced CRC malignancy. Our investigation corroborates that linc01296 functions as an endogenous sponge of miR-26a to regulate mucin1 (MUC1) expression, catalyzed by GALNT3, which modulates the activity of PI3K/AKT pathway. Interestingly, upregulated linc01296 promotes the tumorigensis, liver metastasis and chemoresistance of CRC cell lines in vivo. CONCLUSION: These new findings indicate that linc01296/miR-26a/GALNT3 axis involves in the progression of CRC cells, illuminating the possible mechanism mediated by O-glycosylated MUC1 via PI3K/AKT pathway. This work renders potential diagnostic biomarkers and prospective therapeutic targets for CRC.

LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge.

Long non-coding RNAs (lncRNAs), which are important functional regulators in cancer, have received increased attention in recent years. In this study, next-generation sequencing technology was used to identify aberrantly expressed lncRNAs in follicular thyroid carcinoma (FTC). The long non-coding RNA-HLA complex P5 (HCP5) was found to be overexpressed in FTC. The results of the qPCR analysis were consistent with the sequencing results. In addition, functional experiments showed that overexpression of HCP5 can promote the proliferation, migration, invasiveness and angiogenic ability of FTC cells. Furthermore, according to the sequencing results, HCP5 and alpha-2, 6-sialyltransferase 2 (ST6GAL2) were co-expressed in FTC. We hypothesised that ST6GAL2 may be regulated by HCP5, which would in turn mediate the activity of FTC cells. Through qPCR, immunostaining analyses and functional experiments, we determined that the expression of HCP5 was elevated and was correlated with the levels of ST6GAL2 in FTC tissues and cells. Mechanistic experiments showed that HCP5 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-22-3p, miR-186-5p and miR-216a-5p, which activates ST6GAL2. In summary, our study revealed that HCP5 is a tumour regulator in the development of FTC and that it may contribute to improvement of FTC diagnosis and therapy.

Activated CXCL5-CXCR2 axis promotes the migration, invasion and EMT of papillary thyroid carcinoma cells via modulation of ß-catenin pathway.

Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)-5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as CXCR2-positive cells were used as the cell model. We found that a 24-h stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the migration and invasion of both KTC-1 and B-CPAP cells without affecting their proliferation. The migration- and invasion-promoting effects of rhCXCL5 were attenuated if CXCR2 was silenced by its specific short hairpin RNAs (shRNAs). EMT initiation is defined as downregulation of epithelial-cadherin (E-cadherin) and upregulation of N-cadherin, Vimentin and Snail. Our data showed that rhCXCL5-induced EMT in PTC cells was suppressed by CXCR2 shRNA. Furthermore, the active CXCL5-CXCR2 axis enhanced the phosphorylation of Akt at Ser 473 residue and that of glycogen synthase kinase-3 (GSK-3ß) at Ser 9 residue, and accelerated the nuclear accumulation of ß-catenin in PTC cells. Re-expression of the active form of ß-catenin in PTC cells rescued their impaired invasiveness caused by the blockade of CXCL5-CXCR2 axis. In addition, CXCL5 and CXCR2 were overexpressed in the metastatic lymph nodes obtained from 18 patients with PTC. In summary, our study demonstrates that the activated CXCL5-CXCR2 axis contributes to the metastatic phenotype of PTC cells by modulating Akt/GSK-3ß/ß-catenin pathway.

miR-125a-3p/FUT5-FUT6 axis mediates colorectal cancer cell proliferation, migration, invasion and pathological angiogenesis via PI3K-Akt pathway.

The fucosyltransferase (FUT) family produces glycans, a fundamental event in several cancers, including colorectal cancer (CRC). miR-125a-3p is a non-coding RNA that can reduce cell proliferation and migration in cancer. In this study, we explored the levels of miR-125a-3p and FUT expression in human CRC tissues and two human CRC cell lines by qPCR. The results showed that miR-125a-3p, FUT5 and FUT6 are differentially expressed in normal and tumour tissues. On the basis of our previous research, FUT can be regulated by miRNA, which influences the proliferation and invasion of breast and hepatocellular cancer cells. We hypothesised that FUT5 and FUT6 may be regulated by miR-125a-3p. Luciferase reporter analyses were applied to identify potential target genes of miR-125a-3p. A functional study showed that miR-125a-3p overexpression can inhibit the proliferation, migration, invasion and angiogenesis of CRC cells via down-regulating FUT5 and FUT6. In addition, regulating miR-125a-3p, FUT5 or FUT6 expression markedly modulated the activity of the PI3K/Akt signalling pathway, and this effect of FUT5 or FUT6 could be reversed by transfection with miR-125a-3p-mimics. Taken together, our data suggest that both FUT5 and FUT6 can promote the development of CRC via the PI3K/Akt signalling pathway, which is regulated by miR-125a-3p. miR-125a-3p may serve as a predictive biomarker and a potential therapeutic target in CRC treatment.

Activated platelets inhibit hepatocellular carcinoma cell differentiation and promote tumor progression via platelet-tumor cell binding.

Lack of differentiation in hepatocellular carcinoma (HCC) is associated with increased circulating platelet size. We measured platelet activation and plasma adenosine diphosphate (ADP) levels in HCC patients based on differentiation status. Local platelet accumulation and platelet-hepatoma cell binding were measured using immunohistochemistry (IHC) or flow cytometry. Using a xenograft assay in NON/SCID mice, we tested the effects of the anti-platelet drug clopidogrel on platelet activation, platelet infiltration, platelet-tumor cell binding and tumor cell differentiation. HCC patients with poor differentiation status displayed elevated platelet activation and higher ADP levels. Platelets accumulated within poorly differentiated tissues and localized at hepatoma cell membranes. Platelet-tumor cell binding was existed in carcinoma tissues, largely mediated by P-selectin on platelets. NOD/SCID mice with xenograft tumors also exhibited increased platelet activation and platelet-tumor cell binding. Clopidogrel therapy triggered hepatoma cell differentiation by attenuating platelet activation and platelet-tumor cell binding. TCF4 knockdown promoted HepG-2 cell differentiation and inhibited tumor formation, and TCF4 could be the potential downstream target for clopidogrel therapy.