Circ_0069094 regulates malignant phenotype and paclitaxel resistance in breast cancer cells via targeting the miR-136-5p/YWHAZ axis.

BACKGROUND: Breast cancer is one of the most malignant cancers. Increasing evidence suggests that circular RNAs (circRNAs) are involved in breast cancer progression through sponging microRNA (miRNA). However, the underlying molecular mechanisms of circ_0069094 in breast cancer are unclear. This study aimed to reveal the effect of the circ_0069094/miR-136-5p/tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) pathway on the malignant progression of breast cancer. METHODS: The quantitative real-time polymerase chain reaction and western blot were used to assess the expression of circRNA/miRNA/mRNA. The functional effects of circ_0069094 on the cell processes of breast cancer were investigated by cell counting kit-8, colony-forming assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and transwell invasion assay. The interactions among circ_0069094, miR-136-5p, and YWHAZ were assessed by dual-luciferase reporter assay. A xenograft experiment was performed to determine the effects of circ_0069094 on tumor formation. RESULTS: Circ_0069094 was overexpressed in paclitaxel (PTX)-resistant breast cancer tissues and cells, and the silencing of circ_0069094 decreased tumor growth, cell proliferation and cell invasion while increasing PTX sensitivity and cell apoptosis in PTX-resistant cells. In addition, miR-136-5p was a target of circ_0069094, and miR-136-5p inhibition abolished circ_0069094 knockdown-induced effects in PTX-resistant cells. MiR-136-5p expression was decreased in PTX-resistant breast cancer tissues and cells, and the overexpression of miR-136-5p suppressed the malignant behaviors of breast cancer cells by targeting YWHAZ. Importantly, circ_0069094 regulated YWHAZ expression in breast cancer by targeting miR-136-5p. CONCLUSION: Circ_0069094 silencing improved PTX sensitivity in breast cancer progression through competitively sponging miR-136-5p.

[Progress on eco-technology classification in ecologically vulnerable regions of China]. / æˆ‘å›½ç”Ÿæ€è„†å¼±åŒºç”Ÿæ€æŠ€æœ¯åˆ†ç±»ä½“ç³»ç ”ç©¶è¿›å±•.

Ecological technology is the core of ecological environment governance and restoration in ecologically vulnerable regions. A reasonable classification method is the basis for induction and summary of ecological techno-logy, which is of great significance to classify and solve ecological environmental problems and evaluate the effects of ecological technology implementation. However, there is still no standard method for the classification of ecological technology. From the perspective of ecological technology classification, we summarized the concept of eco-technology and related classification methods, in view of current situation and deficiency of ecological technology related classification, we put forward a system suitable for defining and classifying ecological technology in ecologically vulnerable regions of China, and analyzed the practicality and application prospect. Our review would provide reference for the management and promotion of ecological technology classification.

The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.

The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.

Circ-TFF1 Facilitates Breast Cancer Development via Regulation of miR-338-3p/FGFR1 Axis.

Some circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of breast cancer (BC). We aimed to investigate the role of circRNA trefoil factor 1 (circ-TFF1) in BC progression. The expression of circ-TFF1, microRNA-338-3p (miR-338-3p) and fibroblast growth factor receptor 1 (FGFR1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, and 5-Ethynyl-2'-deoxyuridine (EDU) assays. Cell apoptosis and invasion were assessed by flow cytometry and transwell assay, respectively. Cellular glycolysis, including glucose consumption, lactate production, and ATP/ADP ratio, was detected by commercial kits. All protein levels were measured by western blot assay. The relationship between miR-338-3p and circ-TFF1 or FGFR1 was predicted by online bioinformatics tool and verified by dual-luciferase reporter assay. Xenograft tumor model was established to verify the function of circ-TFF1 in vivo. Circ-TFF1 was overexpressed in BC tissues and cells. Circ-TFF1 knockdown inhibited cell proliferation, invasion and glycolysis and induced apoptosis in BC cells. Circ-TFF1 acted as a sponge of miR-338-3p, and the effects of circ-TFF1 knockdown on BC cell proliferation, apoptosis, invasion, and glycolysis were abolished by miR-338-3p inhibition. FGFR1 was confirmed to be a target gene of miR-338-3p, and miR-338-3p played a tumor-suppressive role in BC by targeting FGFR1. Moreover, circ-TFF1 regulated FGFR1 expression by targeting miR-338-3p. Additionally, circ-TFF1 knockdown hampered tumorigenesis in vivo. Circ-TFF1 knockdown suppressed BC progression by regulating miR-338-3p/FGFR1 axis, providing a promising therapeutic target for BC.

Colorectal cancer (CRC) as a multifactorial disease and its causal correlations with multiple signaling pathways.

Colorectal cancer (CRC) is the third most common malignancy and one of the leading causes of cancer-related death among men worldwide. CRC is a multifactor digestive pathology, which is a huge problem faced not only by clinicians but also by researchers. Importantly, a unique feature of CRC is the dysregulation of molecular signaling pathways. To date, a series of reviews have indicated that different signaling pathways are disordered and have potential as therapeutic targets in CRC. Nevertheless, an overview of the function and interaction of multiple signaling pathways in CRC is needed. Therefore, we summarized the pathways, biological functions and important interactions involved in CRC. First, we investigated the involvement of signaling pathways, including Wnt, PI3K/Akt, Hedgehog, ErbB, RHOA, Notch, BMP, Hippo, AMPK, NF-κB, MAPK and JNK. Subsequently, we discussed the biological function of these pathways in pathophysiological aspects of CRC, such as proliferation, apoptosis and metastasis. Finally, we summarized important interactions among these pathways in CRC. We believe that the interaction of these pathways could provide new strategies for the treatment of CRC.

Downregulation of Krüppel­like factor 1 inhibits the metastasis and invasion of cervical cancer cells.

Cervical cancer is one of the most common malignancies that seriously threatens women's health. Krüppel­like factors (KLFs) have been reported to be associated with the progression of cervical cancer. The role of KLF1 in cervical cancer, which still remains unclear, was investigated in the present study. The expression of KLF1 was detected in different cervical cell lines by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting. Cell proliferation, metastasis and invasion were respectively detected by Cell Counting Kit­8, wound healing and transwell assays. Associated factor expression was also detected by RT­qPCR and western blotting. In addition, the phosphorylation levels of phosphatidylinositol­3­kinase (PI3K) and protein kinase B (Akt) were determined by western blot analysis. The results revealed that KLF1 expression was promoted in SiHa, Caski and C4­1 cervical cancer cells. However, KLF1 knockdown suppressed cell proliferation, metastasis and invasion in SiHa cervical cancer cells. KLF1 knockdown also inhibited the expressions of Ki67, metastasis­associated antigen 1 and matrix metalloproteinase (MMP)­2. KLF1 knockdown promoted the expressions of nonmetastatic clone 23 type 1 and tissue inhibitor of metalloproteinase­2, and the expression of MMP­9 was promoted slightly as well. In addition, KLF1 knockdown inhibited the PI3K/Akt signaling pathway. Hence, it was concluded that KLF1 promoted metastasis and invasion via the PI3K/Akt signaling pathway in cervical cancer cells.

DNA methylation biomarkers for the occurrence of lung adenocarcinoma from TCGA data mining.

The development of lung cancer is a combination of multifactor, multistage, and multiple genetic alterations processes. DNA methylation is an important factor. Currently, the study on the genome-scale epigenetic modification for studying the pathogenesis of lung cancer is still lacking. Here, we aimed to identify the epigenetic modifications of lung cancer, thus to provide scientific basis for the personalized medicine, and research of classification screening for lung adenocarcinoma patients. The DNA methylation data, and the corresponding clinical information of lung adenocarcinoma samples were extracted from the Cancer Genome Atlas (TCGA) database. We explored the association of DNA methylation and gene transcription expression of lung adenocarcinoma by identifying the differentially expressed genes, DNA methylated locis, functional gene clusters, and the relevant genes associated with the survival. We identified 17 differentially expressed genes which had differentially methylated locis, 4 functional gene clusters regulated by methylation, and 522 genes, which were relevant to the survival time of patients. Our study suggested that methylation controlled the gene expression in a variety of ways, which had high/low expression and hyper-/hypo-methylation. Genes of different methylation status showed the different survival curve. The genes and methylated locis identified in this study could be potential biomarkers and therapeutic targets for lung adenocarcinoma.

[Effects of land use/cover change on runoff sediment discharge in typical watershed in Loess gullied-hilly region of China].

By using the measurement technique of dynamic hydrological process and the estimation method of landscape ecology, this paper studied the effects of 1986-2004 land use/cover change (LUCC) on the runoff sediment discharge in the Luoyugou watershed in Tianshui of Gansu Province in third sub-region of Loess Plateau. The results showed that the LUCC in Luoyugou watershed had significant effects on the annual sediment yield. In 1995-2004, the sediment discharge was reduced by approximately 63.0%, compared with that in 1986-1994, and the reduction effect was more significant with increasing annual precipitation. The effects of LUCC on sediment discharge demonstrated seasonal fluctuation characteristic. Relative to that in 1986-1994, the reduction effect of sediment discharge in 1995-2004 was more concentrated in the period from May to October, and, the more the monthly precipitation, the more the reduction of monthly average sediment discharge in 1995-2004 than in 1986-1994. The analysis on precipitation and flood peak discharge frequency indicated that under the same frequency distribution of precipitation intensity, the average sediment concentration in any recurrence period in Luoyugou watershed was smaller in 1995-2004 than in 1986-1994.