Circular RNA CircSLC22A23 Promotes Gastric Cancer Progression by Activating HNRNPU Expression.

BACKGROUND: Circular RNAs (CircRNAs) play essential roles in cancer occurrence as regulatory RNAs. However, circRNA-mediated regulation of gastric cancer (GC) remains poorly understood. AIM: The purpose of this study was to investigate the molecular mechanism of circSLC22A23 (hsa_circ_0075504) underlying GC occurrence. METHODS: CircSLC22A23 levels were first quantified by quantitative real-time reverse transcription-polymerase chain reaction in GC cell lines, 80 paired GC tissues and adjacent normal tissues, and 27 pairs of plasma samples from preoperative and postoperative patients with GC. Then circSLC22A23 was knocked-down with short hairpin RNA to analyze its oncogenic effects on the proliferation, migration, and invasion of GC cells. Finally, circRNA-binding proteins and their downstream target genes were identified by RNA pulldown, mass spectrometry, RNA immunoprecipitation, quantitative real-time reverse transcription-polymerase chain reaction, and Western blot assays. RESULTS: CircSLC22A23 was found to be highly expressed in GC cells, GC tissues, and plasma from GC patients. Knockdown of circSLC22A23 inhibited GC cell proliferation, migration and invasion. RNA pulldown and RNA immunoprecipitation assays verified the interaction between circSLC22A23 and heterogeneous nuclear ribonucleoprotein U (HNRNPU). Knockdown of circSLC22A23 decreased HNRNPU protein levels. Moreover, rescue assays showed that the tumor suppressive effect of circSLC22A23 knockdown was reversed by HNRNPU overexpression. Finally, epidermal growth factor receptor (EGFR) was found to be one of the downstream target genes of HNRNPU that was up regulated by circSLC22A23. CONCLUSION: CircSLC22A23 regulated the transcription of EGFR through activation of HNRNPU in GC cells, suggesting that circSLC22A23 may serve as a potential therapeutic target for the treatment of GC.

Aquatic Bacteria Rheinheimera tangshanensis New Ability for Mercury Pollution Removal.

To explore the strong tolerance of bacteria to Hg pollution, aquatic Rheinheimera tangshanensis (RTS-4) was separated from industrial sewage, with a maximum Hg(II) tolerant concentration of 120 mg/L and a maximum Hg(II) removal rate of 86.72 ± 2.11%, in 48 h under optimum culture conditions. The Hg(II) bioremediation mechanisms of RTS-4 bacteria are as follows: (1) the reduction of Hg(II) through Hg reductase encoded by the mer operon; (2) the adsorption of Hg(II) through the production of extracellular polymeric substances (EPSs); and (3) the adsorption of Hg(II) using dead bacterial biomass (DBB). At low concentrations [Hg(II) ≤ 10 mg/L], RTS-4 bacteria employed Hg(II) reduction and DBB adsorption to remove Hg(II), and the removal percentages were 54.57 ± 0.36% and 45.43 ± 0.19% of the total removal efficiency, respectively. At moderate concentrations [10 mg/L < Hg(II) ≤ 50 mg/L], all three mechanisms listed above coexisted, with the percentages being 0.26 ± 0.01%, 81.70 ± 2.31%, and 18.04 ± 0.62% of the total removal rate, respectively. At high concentrations [Hg(II) > 50 mg/L], the bacteria primary employed EPS and DBB adsorption to remove Hg(II), where the percentages were 19.09 ± 0.04% and 80.91 ± 2.41% of the total removal rate, respectively. When all three mechanisms coexisted, the reduction of Hg(II) occurred within 8 h, the adsorption of Hg(II) by EPSs and DBB occurred within 8-20 h and after 20 h, respectively. This study provides an efficient and unused bacterium for the biological treatment of Hg pollution.

Hsa_circ_0001020 Serves as a Potential Biomarker for Gastric Cancer Screening and Prognosis.

Circular RNAs (circRNAs) are an intriguing class of RNAs with covalently closed-loop structures. With characteristics of high stability and disease-specific expression, circRNAs are emerging as ideal targets for cancer therapy. However, the screening utility and clinical value of circRNAs in gastric cancer (GC) remain largely elusive. We detected levels of hsa_circ_0001020 in cell lines and tissue and plasma samples and investigated its clinicopathological correlations. Kaplan-Meier survival curves and regression analyses were used to analyze its prognostic value. Receiver operating characteristic curves and biomarker combinations were examined to verify its screening value. Bioinformatics analysis was also performed to predict potential biological functions. Our tests found that hsa_circ_0001020 was significantly upregulated in GC cell lines, GC tissue samples, and even in plasma. High hsa_circ_0001020 expression levels in GC tissues were significantly associated with distal metastasis and blood carbohydrate antigen 19-9 (CA19-9). GC patients with high hsa_circ_0001020 had a lower overall survival and disease-free survival time than the low levels. Regression analysis suggested that the level of hsa_circ_0001020 expression was an independent prognostic factor for survival time. As a biomarker for GC, hsa_circ_0001020 showed a superior AUC, sensitivity, and specificity than carcinoembryonic antigen and CA19-9, and was suitable for combination with clinical tumor biomarkers. Bioinformatics analysis provided valuable clues for the possible oncogenic pathways of GC, such as the FoxO and p53 signaling pathways. In conclusion, our study found that hsa_circ_0001020 in GC could be a reliable biomarker to screen for GC and predict prognosis.

The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway.

BACKGROUND: Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer. METHODS: The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis. RESULTS: Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p. CONCLUSION: By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.

Hsa_circ_0003195 as a biomarker for diagnosis and prognosis of gastric cancer.

PURPOSE: Recent studies have shown that circular RNAs (circRNAs) are closely related to the occurrence and development of gastric cancer. In this paper, we analyzed the value of hsa_circ_0003195 in diagnosis and prognosis of gastric cancer. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the level of hsa_circ_0003195 in 100 paired gastric cancer tissues and paracancerous tissues, 74 paired fasting plasma from gastric cancer patients before and 10 days after operation, and 74 fasting plasmas from healthy controls. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic value. The survival analysis and Cox proportional-hazards model were used to evaluate the efficiency of hsa_circ_0003195 in predicting overall survival (OS) in patients with gastric cancer. RESULTS: The expression of hsa_circ_0003195 was down-regulated in gastric cancer tissues and plasma from patients with gastric cancer. The expression level of hsa_circ_0003195 was correlated with differentiation, TNM stages, lymphatic metastasis, and distal metastasis. The area under the ROC curve (AUC) of tissue and plasma hsa_circ_0003195 was 0.684 and 0.695, respectively. The plasma hsa_circ_0003195 can be used as predictors of survival of patients with gastric cancer. CONCLUSION: Hsa_circ_0003195 may be a new diagnostic and prognostic marker of gastric cancer.

The roles and mechanisms of circular RNAs related to mTOR in cancers.

BACKGROUND: Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis. METHODS: All data were collected through PubMed and CNKI, using terms including "circRNA," "mTOR," "caner," "signaling pathway," "biomarker," "diagnosis," "treatment." Articles published in Chinese and English were included. RESULTS: In this review, the expression, function, and mechanism of circRNA-associated mTOR in cancers were described. CircRNA-associated-mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen-activated protein kinase (MAPK)/mTOR, and AMP-activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS-7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ-IARS and circRHOBTB3), renal carcinoma (ciRS-7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ-ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ-MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ-PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application.

BACKGROUND: Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. METHODS: Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan-Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. RESULTS: Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease-free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease-free survival time. The nomograms showed good accuracy of predicting survival time. CONCLUSION: Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced-stage patients.

Establishment of an Absolute Quantitative Method to Detect a Plasma tRNA-Derived Fragment and Its Application in the Non-Invasive Diagnosis of Gastric Cancer.

(1) Transfer RNA (tRNA)-derived fragments (tRFs) are a new category of regulatory non-coding RNAs with distinct biological functions in cancer. They are produced from pre-tRNAs or mature tRNAs and their sequences are relatively short; thus, the amplification of tRFs, especially those in body fluids, is faced with certain technical difficulties. In this study, we established a quantitative method to detect plasma tRF-27-87R8WP9N1E5 (tRF-27) and used it to screen gastric cancer patients. (2) A specific stem-loop-structure reverse transcription primer, a TaqMan probe, and amplification primers for tRF-27 were prepared, and the absolute quantitative method was used to measure plasma tRF-27 levels. To determine the noninvasive diagnostic value of tRF-27 in gastric cancer, plasma tRF-27 levels in patients with benign and malignant lesions (120 healthy individuals, 48 patients with benign lesions, 48 patients with precancerous lesions, and 72 patients with early gastric cancer) were analyzed. Plasma tRF-27 levels were also analyzed in 106 preoperative gastric cancer patients, 106 postoperative gastric cancer patients, and 120 healthy individuals. Survival curves and Cox regression models were established and analyzed. (3) A new absolute quantitative method to determine the plasma tRF-27 copy number was established. Plasma tRF-27 levels were significantly increased in gastric cancer patients compared to healthy individuals, and the area under the receiver operating characteristic curve was 0.7767, when the cutoff value was 724,807 copies/mL, with sensitivity and specificity values of 0.6226 and 0.8917, respectively. The positive predictive and negative predictive values were 83.50% and 72.80%, respectively. Plasma tRF-27 levels in postoperative gastric cancer patients were significantly decreased compared to preoperative gastric cancer patients and tended to the levels of healthy individuals. Moreover, tRF-27 levels were closely related to tumor size and Ki67 expression in gastric cancer patients. Prognostic analysis showed that tRF-27 may be an independent predictor of overall survival. (4) This novel and non-invasive method of measuring plasma tRF-27 levels was valuable in the early diagnosis of gastric cancer.

Observational Study of Ground-Level Ozone in the Desert Atmosphere.

Arid lands such as deserts cover more than 35% of the Earth's land surface. Concerns regarding ground-level O3 pollution have been widely addressed in many regions in China, but the behavior of the O3 cycles in the desert atmosphere remains poorly understood. An 8-year observation was conducted to investigate the long-term temporal O3 variations in the atmosphere of the Taklimakan Desert, western China. The results showed that the diurnal and seasonal variations of O3 were mainly influenced by natural processes such as temperature, leading to a different temporal pattern compared with other Chinese regions under the intensive influence of anthropogenic activities. Moreover, the long-term pattern indicates that there exists decoupling trends of O3 variations between our study site (i.e., decreasing trend) and the developed regions in China (i.e., increasing trend). Knowledge of the temporal O3 patterns could therefore provide crucial insights for future effective O3 control strategies in China.

Vertical distribution characteristics of soil mercury and its formation mechanism in permafrost regions: A case study of the Qinghai-Tibetan Plateau.

Continuing permafrost degradation is increasing the risk of mercury (Hg) exposure in the permafrost regions on the Qinghai-Tibetan Plateau (QTP), but related studies are still limited, especially the ones on the detailed Hg migration processes in permafrost. The vertical distribution characteristics of soil Hg were investigated in three ecosystems in the Beiluhe area on the QTP, and its influencing factors and formation mechanism were investigated. The results indicate that the total soil mercury (THg) concentration in the Beiluhe area remains at an extremely low level (6.33 ± 2.45 ng/g). In the vertical profile, the THg concentration of the shallow soil layer (0-50 cm) (5.96 ± 2.22 ng/g) is significantly lower than that of the deep layer (50-400 cm) (7.44 ± 2.71 ng/g) (p < 0.05). Within the upper 50 cm, the THg concentration decreases with soil depth, and the peak THg concentration occurs at 100-300 cm on the entire profile. Although the THg concentration is slightly affected by the organic matter in the shallow soil layer, in general, the soil parent material is the dominant factor affecting the THg concentration. Intense weathering results in a low THg concentration in the shallow soil layer because the soil Hg is carried downward with the soil moisture. To a certain depth, the impermeable frozen soil layer intercepts the flow of the soil Hg, and it forms a Hg enrichment layer. This paper presents the distinctive pattern of the soil Hg distribution in the permafrost regions of the QTP.

Nitrogenous and carbonaceous aerosols in PM2.5 and TSP during pre-monsoon: Characteristics and sources in the highly polluted mountain valley.

This study reports for the first time a comprehensive analysis of nitrogenous and carbonaceous aerosols in simultaneously collected PM2.5 and TSP during pre-monsoon (March-May 2018) from a highly polluted urban Kathmandu Valley (KV) of the Himalayan foothills. The mean mass concentration of PM2.5 (129.8 µg/m3) was only ~25% of TSP mass (558.7 µg/ m3) indicating the dominance of coarser mode aerosols. However, the mean concentration as well as fractional contributions of water-soluble total nitrogen (WSTN) and carbonaceous species reveal their predominance in find-mode aerosols. The mean mass concentration of WSTN was 17.43±4.70 µg/m3 (14%) in PM2.5 and 24.64±8.07 µg/m3 (5%) in TSP. Moreover, the fractional contribution of total carbonaceous aerosols (TCA) is much higher in PM2.5 (~34%) than that in TSP (~20%). The relatively low OC/EC ratio in PM2.5 (3.03 ± 1.47) and TSP (4.64 ± 1.73) suggests fossil fuel combustion as the major sources of carbonaceous aerosols with contributions from secondary organic aerosols. Five-day air mass back trajectories simulated with the HYSPLIT model, together with MODIS fire counts indicate the influence of local emissions as well as transported pollutants from the Indo-Gangetic Plain region to the south of the Himalayan foothills. Principal component analysis (PCA) also suggests a mixed contribution from other local anthropogenic, biomass burning, and crustal sources. Our results highlight that it is necessary to control local emissions as well as regional transport while designing mitigation measures to reduce the KV's air pollution.

Hf-Nd-Sr Isotopic Composition of the Tibetan Plateau Dust as a Fingerprint for Regional to Hemispherical Transport.

Large areas of arid regions in the Tibetan Plateau (TP) are undergoing desertification and subsequent aeolian emission and transport. The contribution of TP soils to the atmospheric aerosol burden in Asia and elsewhere is not known. Here, we use Hf, Nd, and Sr isotopes to distinguish the TP from other Asian dust-producing regions and compare the signatures to sediments in major dust sink regions. We found that the Hf-Nd-Sr isotopes of TP soils showed unique spatial signatures. From north to south, 87Sr/86Sr ratios gradually increased, while εNd and εHf values gradually decreased; from west to east, 87Sr/86Sr and εHf gradually increased, while εNd changed indistinctly. The Hf-Nd-Sr isotopic compositions of TP soils were controlled by four geographic isotope regions: the northern, southern, western, and eastern TP. Compared with Asian large deserts, the TP showed a unique isotopic composition, which together exhibited a significant spatial change across Asia. Compared to dust isotopes in prominent sink areas, we found that the TP is an important dust source to eastern TP glaciers, the Chinese Loess Plateau, South China Sea, Japan, and Greenland. This study provides clear isotopic evidence that the TP is a major aeolian contributor in the Northern Hemisphere and may have important implications for the global aeolian cycle.

Observation-Based Mercury Export from Rivers to Coastal Oceans in East Asia.

Globally, the consumption of coastal fish is the predominant source of human exposure to methylmercury, a potent neurotoxicant that poses health risks to humans. However, the relative importance of riverine inputs and atmospheric deposition of mercury into coastal oceans remains uncertain owing to a lack of riverine mercury observations. Here, we present comprehensive seasonal observations of riverine mercury and methylmercury loads, including dissolved and particulate phases, to East Asia's coastal oceans, which supply nearly half of the world's seafood products. We found that East Asia's rivers annually exported 95 ± 29 megagrams of mercury to adjacent seas, 3-fold greater than the corresponding atmospheric deposition. Three rivers alone accounted for 71% of East Asia's riverine mercury exports, namely: Yangtze, Yellow, and Pearl rivers. We further conducted a metadata analysis to discuss the mercury burden on seawater and found that riverine export, combined with atmospheric deposition and terrestrial nutrients, quantitatively elevated the levels of total, methylated, and dissolved gaseous mercury in seawater by an order of magnitude. Our observations support that massive amounts of riverine mercury are exported to coastal oceans on a continental scale, intensifying their spread from coastal seawater to the atmosphere, marine sediments, and open oceans. We suggest that the impact of mercury transport along the land-ocean aquatic continuum should be considered in human exposure risk assessments.

Global profile of tRNA-derived small RNAs in gastric cancer patient plasma and identification of tRF-33-P4R8YP9LON4VDP as a new tumor suppressor.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been found to play important roles in the occurrence and development of cancers. However, the tsRNA profile in gastric cancer is unknown. In this study, we aimed to identify the global tsRNA profile in plasma from gastric cancer patients and elucidate the role of tRF-33-P4R8YP9LON4VDP in gastric cancer. Differentially expressed tsRNAs in the plasma of gastric cancer patients and healthy controls were investigated using RNA sequencing. The expression levels of tRF-33-P4R8YP9LON4VDP in the plasma of gastric cancer patients, healthy controls and gastric cancer cell lines were first detected by quantitative reverse transcription-polymerase chain reaction. The effects of tRF-33-P4R8YP9LON4VDP overexpression or downregulation in gastric cancer cells on proliferation, migration, apoptosis, and cell cycle were analyzed using the Cell Counting Kit-8, scratch assay, Transwell assay, and flow cytometry, respectively. There were 21 upregulated and 46 downregulated tsRNAs found in plasma from gastric cancer patients. The significantly upregulated tsRNAs included tRF-18-S3M83004, tRF-31-PNR8YP9LON4VD, tRF-19-3L7L73JD, tRF-33-P4R8YP9LON4VDP, tRF-31-PER8YP9LON4VD, tRF-18-MBQ4NKDJ, and tRF-31-PIR8YP9LON4VD. The significantly downregulated tsRNAs included tRF-41-YDLBRY73W0K5KKOVD, tRF-18-07QSNHD2, tRF-28-86J8WPMN1E0J, tRF-29-86V8WPMN1EJ3, tRF-31-6978WPRLXN4VE, tRF-30-MIF91SS2P46I, tRF-26-MI7O3B1NR8E, tRF-30-RRJ89O9NF5W8, tRF-26-XIP2801MK8E, and tRF-35-V0J8O9YEKPRS93, In vitro studies showed that tRF-33-P4R8YP9LON4VDP inhibited proliferation of gastric cancer cells. In conclusion, tsRNAs such as tRF-33-P4R8YP9LON4VDP could serve as a novel diagnostic biomarker and target for gastric cancer therapeutics.

Concentration, sources and wet deposition of dissolved nitrogen and organic carbon in the Northern Indo-Gangetic Plain during monsoon.

Precipitation represents an important phenomenon for carbon and nitrogen deposition. Here, the concentrations and fluxes of dissolved organic carbon (DOC) and total dissolved nitrogen (TDN) with their potential sources were analyzed in wet precipitation during summer monsoon from the Northern Indo-Gangetic Plain (IGP), important but neglected area. The volume-weighted mean (VWM) concentration of DOC and TDN were 687.04 and 1210.23 µg/L, respectively. Similarly, the VWM concentration of major ions were in a sequence of NH4+ > Ca2+ > SO42- > Na+ > K+ > NO3- > Cl- > Mg2+ > F- > NO2-, suggesting NH4+ and Ca2+ from agricultural activities and crustal dust played a vital role in precipitation chemistry. Moreover, the wet deposition flux of DOC and TDN were 9.95 and 17.06 kg/(ha⋅year), respectively. The wet deposition flux of inorganic nitrogen species such as NH4+-N and NO3--N were 14.31 and 0.47 kg/(ha⋅year), respectively, demonstrating the strong influence of emission sources and precipitation volume. Source attribution from different analysis suggested the influence of biomass burning on DOC and anthropogenic activities (agriculture, animal husbandry) on nitrogenous species. The air-mass back trajectory analysis indicated the influence of air masses originating from the Bay of Bengal, which possibly carried marine and anthropogenic pollutants along with the biomass burning emissions to the sampling site. This study bridges the data gap in the less studied part of the northern IGP region and provides new information for policy makers to deal with pollution control.

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer.

BACKGROUND: KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by KLF5 in CRC are currently unknown. METHODS: In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. RESULTS: We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. CONCLUSIONS: In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC.

Vegetation Mediated Mercury Flux and Atmospheric Mercury in the Alpine Permafrost Region of the Central Tibetan Plateau.

Measurements of land-air mercury (Hg) exchanges over vegetated surfaces are needed to further constrain Hg fluxes over vegetated terrestrial surfaces. Yet, knowledge of land-air Hg dynamics in alpine grasslands remains poor. Hg fluxes over an alpine meadow were measured throughout a full vegetation period in the central Tibetan Plateau (TP). This TP grassland served as a small source of atmospheric total gaseous Hg (TGM) during vegetation period (0.92 µg m-2). Hg fluxes decreased logarithmically during plant growing season, resulting from the influence of vegetation by light shading and plant Hg uptake, although the latter might be minor due to low biomass at this site. Temporal patterns of TGM indicated the importance of land-air dynamics in regulating TGM levels. During the plant emergence, diel pattern of TGM covaried with Hg emission fluxes resulting in lower concentrations at night and higher concentrations in afternoon. During all other vegetation stages, TGM showed minima before dawn and "morning peak" shortly after sunrise, in conjunction with corresponding Hg fluxes showing sink before dawn and source after sunrise. Moreover, TGM concentrations showed a decreasing trend with plant growing, further indicating the role of vegetation in driving seasonal TGM variations by regulating land-air Hg dynamics.

Decoupling Natural and Anthropogenic Mercury and Lead Transport from South Asia to the Himalayas.

Mercury (Hg) and lead (Pb) accumulation since the Industrial Revolution has been generally observed to increase concurrently in lake sedimentary records around the world. Located downwind during the monsoon season from the rapidly developing South Asia, the Himalayas and the Tibetan Plateau are expected to receive direct anthropogenic Hg and Pb loadings, yet the source, pathway, and effects of such transport remain poorly known due to logistic challenges in accessing this region. When studying the sediment record from Lake Gokyo (4750 m above sea level (a.s.l.)) in the Himalayas, we find remarkably different Hg and Pb accumulation trends over the past 260 years. Although Hg accumulation has continued to increase since the Industrial Revolution, Pb accumulation peaked during that time and has been decreasing since then. Stable isotope analysis reveals that the decoupling trends between these two elements are due to different sources and pathways of Hg and Pb in the region. Both δ202Hg and Δ199Hg have been increasing since the Industrial Revolution, suggesting that anthropogenic Hg emissions from South Asia have been continuously increasing and that the Indian monsoon-driven wet deposition of atmospheric Hg is the dominant pathway for Hg accumulation in the sediments. In contrast, analysis of 206Pb/207Pb and 208Pb/207Pb ratios suggests that Pb accumulation in the sediments originates primarily from natural sources and that the decreasing trend of Pb accumulation is most likely due to a weakening input of atmospheric mineral dust by the westerlies. These decoupling trends highlight the ongoing issue of transboundary Hg transport to the Himalayas and the Tibetan Plateau that are source waters for major freshwater systems in Asia and calls for regional and international collaborations on Hg emission controls in South Asia.

Novel potential tumor biomarkers: Circular RNAs and exosomal circular RNAs in gastrointestinal malignancies.

BACKGROUND: Circular RNAs (circRNAs) are structural ubiquitous RNA molecules. Accumulating evidences have elucidated that circRNAs play essential roles in the pathogenesis of diseases including cancers. Exosomal circRNAs are those circRNAs stably existing in exosomes and having high clinical values as novel potential diagnostic biomarkers of many diseases. Gastrointestinal (GI) malignancies, including pancreatic cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer, are leading causes of mortality worldwide and a major global health burden. However, no ideal tumor biomarkers of screening early GI cancers are currently available. METHODS: We collected data through Web of Science. The search terms used were as follows: circular RNA, circRNA, exosomes, exosomal circRNAs, biomarkers, gastrointestinal malignancies, pancreatic cancer, hepatocellular carcinoma, HCC, gastric cancer, colorectal cancer, physiological functions, biogenesis, molecular mechanism. Only articles published in English were included. RESULTS: We found that several circRNAs and exosomal circRNAs have been used as potential biomarkers to screen GI cancers including pancreatic cancer (hsa_circ_0001649, circ_0007534, circ_0030235, circRHOT1, circZMYM2, circ-LDLRAD3, chr14:101402109-101464448C, chr4:52729603-52780244C, circ-IARS, and circ-PDE8A), HCC (circSETD3, circADAMTS13, hsa_circ_0007874, hsa_circ_104135, circFBLIM1, cSMARCA5, circRNA-100338, and circPTGR1), colorectal cancer (hsa_circ_0001178, hsa_circ_0000826, hsa_circ_0004771, circDDX17, circITGA7, and circHIPK3), and gastric cancer (hsa_circ_0074362, circNRIP1, circAKT3, circ-DONSON, circPSMC3, circ-KIAA1244, circPVRL3, circPVT1, hsa_circ_0000096, ciRS-133, hsa_circ_0001017, and hsa_circ_0061276). CONCLUSION: CircRNAs and exosomal circRNAs have the potential high clinical diagnostic values for GI malignancies.

Reduced expression of circRNA hsa_circ_0067582 in human gastric cancer and its potential diagnostic values.

BACKGROUND: Gastric cancer (GC) is one of the global mortality diseases and has a poor prognosis due to the lack of ideal tumor biomarkers. Circular RNAs (circRNAs) are an abundant kind of endogenous RNAs that recently are found play a crucial role in the cancer occurrence and development. Nevertheless, little is known with regard to the diagnostic values of these circRNAs for GC. In this article of research, we investigated the role of hsa_circ_0067582 in clinical diagnosis of GC. MATERIALS AND METHODS: We used divergent primers, and the expression levels of hsa_circ_0067582 in 93 fresh GC tissues and paired adjacent normal tissues from surgical patients were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, a receiver operating characteristic (ROC) curve was established to assess the diagnostic significance of hsa_circ_0067582. The relationship between expression of hsa_circ_0067582 and clinicopathological factors of patients was made further explored. RESULTS: Hsa_circ_0067582 levels were significantly decreased in GC tissues contrasted with adjacent normal tissues (n = 93, P < .001). After that, we discovered that it was evidently downregulated in 81.7% (76/93) GC tissues. The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.6937, the sensitivity was 66.67%, and the specificity was 61.29%. Moreover, the hsa_circ_0067582 levels were obviously associated with tumor diameter (P = .002) and carbohydrate antigen 19-9 (CA19-9, P = .01). Meanwhile, after operation, low-level group of hsa_circ_0067582 of GC patients was associated with better prognosis. CONCLUSION: Our data imply that hsa_circ_000067582 may be a potential biomarker for GC diagnosis and prognosis evaluation.