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It is well recognized that hypoxia-inducible factor 1 alpha (HIF-1α) is involved in cancer metastasis, chemotherapy and poor prognosis. We previously found that deferoxamine, a hypoxia-mimetic agent, induces epithelial-mesenchymal transition (EMT) in colorectal cancer. Therefore, here we explored a new molecular mechanism for HIF-1α contributing to EMT and cancer metastasis through binding to ZEB1. In this study, we showed that overexpression of HIF-1α with adenovirus infection promoted EMT, cell invasion and migration in vitro and in vivo. On a molecular level, HIF-1α directly binding to the proximal promoter of ZEB1 via hypoxia response element (HRE) sites thus increasing the transactivity and expression of ZEB1. In addition, inhibition of ZEB1 was able to abrogate the HIF-1α-induced EMT and cell invasion. HIF-1α expression was highly correlated with the expression of ZEB1 in normal colorectal epithelium, primary and metastatic CRC tissues. Interestingly, both HIF-1α and ZEB1 were positively associated with Vimentin, an important mesenchymal marker of EMT, whereas negatively associated with E-cadherin expression. These findings suggest that HIF-1α enhances EMT and cancer metastasis by binding to ZEB1 promoter in CRC. HIF-1α and ZEB1 are both widely considered as tumor-initiating factors, but our results demonstrate that ZEB1 is a direct downstream of HIF-1α, suggesting a novel molecular mechanism for HIF-1α-inducing EMT and cancer metastasis.

This study investigates the complex dynamic behavior of three-tailed helical microrobots operating in confined spaces. A stochastic dynamic model has been developed to analyze the effects of input angular velocity, current, fluid viscosity, and channel width on their motion trajectories, velocity, mean squared displacement (MSD), and wobbling rate. The results indicate that Gaussian white noise exerts a dispersive driving effect on the motion characteristics of the microrobots, leading to a 49% reduction in their velocity compared to deterministic conditions. Additionally, the time required for microrobots to traverse from the initial position to the bifurcation point decreases by 65% when the current is increased and by 39% when the fluid viscosity is reduced. These findings underscore the importance of optimizing control parameters to effectively mitigate noise impacts, enhancing the practical performance of the microrobots in real-world applications. This research offers solid theoretical support and guidance for the deployment of microrobots in complex environments.

Land degradation significantly impacts regional economic development and food security, particularly in arid river basins where soil and water conservation is crucial. Understanding the extent and causes of land degradation is pivotal for effectively prevention and management. This study employs the soil adjusted vegetation index (SAVI), the temperature vegetation dryness index (TVDI), and the salinization detection index (SDI), combined with the analytic hierarchy process and the entropy weight method, to construct a comprehensive land degradation index (LDI). Sen’s slope trend analysis and the Mann-Kendall significance test were used to analyze land degradation trends in the Ebinur Lake watershed from 2002 to 2022. Additionally, the optimal parameters-based geographical detector was used to examine the underlying mechanisms of land degradation. The results indicate the following: (1) From 2002 to 2012, the degree of land degradation in the Ebinur Lake watershed worsened, particularly in the eastern and southeastern parts, as well as in the southern region of Toli County. From 2012 to 2022, land degradation significantly improved, with a notable reduction in degraded land area. (2) Over the period of 2002-2022, 93.08 % of the land in the research region exhibited a declining LDI trend, 3.95 % showed no change, and only 2.96 % showed an increasing LDI trend. (3) Moderate, severe, and very severe degradation mainly occurred on grassland and unused land, while light degradation and non-degradation primarily occurred on forest land and cultivated land. (4) Unreasonable land use and overgrazing were identified as the primary factors influencing land degradation, with elevation being a secondary factor. The interaction between land use and other factors was found to be most significant, followed by the synergistic effects of grazing quantity with elevation, annual average temperature, gross domestic product, soil moisture, and elevation with annual average precipitation, and temperature. The results of this study offer an empirical basis and taking decisions assistance for land degradation control in the Ebinur Lake Basin, as well as examples and references for assessing land degradation in other places.

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.

It has been demonstrated that microRNA-192 (miR-192) serves important roles in different cancer types, including breast cancer, prostate cancer and colorectal cancer. However, its biological role and function in breast cancer remains largely unknown. The present study aimed to determine the role of miR-192 in breast cancer. In the present study, one normal breast and two breast tumor cells lines were used, which included the normal mammary fibroblast cell line Hs578Bst, a more aggressive breast tumor cell line MDA-MB-231 and a less aggressive breast tumor cell line MCF-7. The effect of miR-192 on proliferation of breast cancer cells was detected with an MTT assay. Western blot analysis was performed to determine protein expression of caveolin 1 (CAV1). A lentiviral vector that overexpresses pre-miR-192 and control lentiviral packaging plasmids were used in the present study. The Student's t-test was performed to analyze the significance of differences between samples. In the present study, it was determined that the expression of miR-192 is downregulated in breast cancer, compared with the adjacent normal tissues. Overexpression of miR-192 significantly inhibited cell proliferation, and induced cell apoptosis and cell cycle arrest in MCF7 and MDA-MB-231 cells. Using a bioinformatics method, CAV1 was considered a potential target of miR-192. Furthermore, it was demonstrated that CAV1 is a direct target of miR-192 and its protein expression is negatively regulated by miR-192. Therefore, the present study demonstrated that miR-192 serves an important role as a regulator in breast cancer and the miR-192/CAV1 axis has a potential as a therapeutic target for treatment of breast cancer.

It has been demonstrated that microRNA-192 (miR-192) serves important roles in different cancer types, including breast cancer, prostate cancer and colorectal cancer. However, its biological role and function in breast cancer remains largely unknown. The present study aimed to determine the role of miR-192 in breast cancer. In the present study, one normal breast and two breast tumor cells lines were used, which included the normal mammary fibroblast cell line Hs578Bst, a more aggressive breast tumor cell line MDA-MB-231 and a less aggressive breast tumor cell line MCF-7. The effect of miR-192 on proliferation of breast cancer cells was detected with an MTT assay. Western blot analysis was performed to determine protein expression of caveolin 1 (CAV1). A lentiviral vector that overexpresses pre-miR-192 and control lentiviral packaging plasmids were used in the present study. The Student's t-test was performed to analyze the significance of differences between samples. In the present study, it was determined that the expression of miR-192 is downregulated in breast cancer, compared with the adjacent normal tissues. Overexpression of miR-192 significantly inhibited cell proliferation, and induced cell apoptosis and cell cycle arrest in MCF7 and MDA-MB-231 cells. Using a bioinformatics method, CAV1 was considered a potential target of miR-192. Furthermore, it was demonstrated that CAV1 is a direct target of miR-192 and its protein expression is negatively regulated by miR-192. Therefore, the present study demonstrated that miR-192 serves an important role as a regulator in breast cancer and the miR-192/CAV1 axis has a potential as a therapeutic target for treatment of breast cancer.

Deferoxamine (DFX), a metal chelator, has been previously reported to induce hypoxia and hypoxia-inducible factor-1α (HIF-1α) expression. HIF-1α is a common inducer of epithelial-mesenchymal transition (EMT) in many solid tumors. However, the effect of DFX on cancer metastasis and the related mechanisms are not well established. In the present study, we aimed to ascertain whether DFX enhances EMT and cancer metastasis in colorectal cancer. After confirmation of DFX-inducing HIF-1α expression, we examined the effect of DFX on cell adhesion, migration and invasion abilities and found a positive effect on the above functions. Consequently, cell morphology, cell growth and expression of EMT markers were assessed in cells with or without DFX treatment. We found that cells exposed to DFX were more isolated. They were spindle-shaped and looked similar to fibroblast-like cells, accompanied by increased anchorage-independent growth. DFX-treated cells expressed E-cadherin and plakoglobin at a higher level, and vimentin and N-cadherin at a lower level, when compared with these levels in control cells. Furthermore, the expression of E-cadherin in the cell membrane was markedly decreased in DFX-treated cells. These results suggest that DFX promotes cancer migration and invasion via a process consistent with EMT in colorectal cancer.

It is well recognized that hypoxia-inducible factor 1 alpha (HIF-1[alpha]) is involved in cancer metastasis, chemotherapy and poor prognosis. We previously found that deferoxamine, a hypoxia-mimetic agent, induces epithelial-mesenchymal transition (EMT) in colorectal cancer. Therefore, here we explored a new molecular mechanism for HIF-1[alpha] contributing to EMT and cancer metastasis through binding to ZEB1. In this study, we showed that overexpression of HIF-1[alpha] with adenovirus infection promoted EMT, cell invasion and migration in vitro and in vivo. On a molecular level, HIF-1[alpha] directly binding to the proximal promoter of ZEB1 via hypoxia response element (HRE) sites thus increasing the transactivity and expression of ZEB1. In addition, inhibition of ZEB1 was able to abrogate the HIF-1[alpha]-induced EMT and cell invasion. HIF-1[alpha] expression was highly correlated with the expression of ZEB1 in normal colorectal epithelium, primary and metastatic CRC tissues. Interestingly, both HIF-1[alpha] and ZEB1 were positively associated with Vimentin, an important mesenchymal marker of EMT, whereas negatively associated with E-cadherin expression. These findings suggest that HIF-1[alpha] enhances EMT and cancer metastasis by binding to ZEB1 promoter in CRC. HIF-1[alpha] and ZEB1 are both widely considered as tumor-initiating factors, but our results demonstrate that ZEB1 is a direct downstream of HIF-1[alpha], suggesting a novel molecular mechanism for HIF-1[alpha]-inducing EMT and cancer metastasis.

FHL2 (Four and a half LIM-only protein 2) has been identified as an oncogene in colon cancer and suppression of FHL2 induces cell differentiation and tumorigenesis in colon cancer cell lines. The aim of this study was to develop a novel and effective approach to knockdown FHL2, which can serve as a promising target of colon cancer therapy. Recombinant adeno-associated virus (rAAV) was generated bearing with FHL2-shRNA and transfected into LoVo cells. Cell cycle and growth were assessed. The interaction between FHL2 and G0/G1 cell cycle and growth was evaluated by flow cytometry, western blot analysis and WST-1 assay. We showed that suppression of FHL2 by rAAV-shRNA induced G0/G1 cell cycle arrest and inhibited cell growth. Apoptosis-related proteins and their activity was investigated at the same time. rAAV-FHL2-shRNA activated intrinsic and extrinsic apoptotic pathways and increased cell susceptibility to apoptotic stimuli by 5-FU. Moreover, a xenograft model was established to explore rAAV-FHL2-shRNA with 5-FU mediated tumorigenesis in vivo. A strong anti-tumorigenic effect of rAAV-FHL2-shRNA was shown in nude mice and this antitumor effect was enhanced when combined with 5-FU treatment. These findings implicate FHL2 as a cell cycle and growth modulator and thus inhibit apoptosis in colon cancer cells. rAAV-shRNA-FHL2 may serve as a novel and potent therapeutic or 5-FU co-therapeutic agent for colon cancer.

KLF8 is a member of the KLF transcription factor family that plays an important role in oncogenesis. However, the role of KLF8 in colorectal cancer remains unknown. The aims of the present study were to examine KLF8 expression in colorectal cancers, to determine the role of KLF8 in cell differentiation and to investigate the antiproliferative effect of KLF8 silencing. The expression of KLF8 and phospho-ERK proteins was analyzed, and the effects of KLF8 suppression on cell differentiation and growth were evaluated. In addition, the biological impact of KLF8 knockdown on colorectal cancer cells was investigated in vitro and in vivo. The expression of the KLF8 protein was higher in 10/14 (71.43%) fresh cancer tissues compared with adjacent normal tissues, and the blockade of ERK signaling by U0126 decreased the expression of KLF8 in a time- and dose-dependent manner. Furthermore, KLF8-siRNA induced the expression of carcinoembryonic antigen (CEA) and E-cadherin as well as the maturation of F-actin. KLF8 suppression inhibited serum-dependent, anchorage-dependent and -independent cell growth. Moreover, KLF8 silencing induced apoptosis and sensitized cancer cells to 5-fluorouracil (5-FU). A strong antitumorigenic effect by lenti-KLF8-shRNA, which was enhanced when combined with 5-FU treatment, was exerted in nude mice. Thus, KLF8 suppression induced cell differentiation and inhibited tumorigenesis.