miR-451a suppresses the proliferation and migration of high-grade serous ovarian cancer by targeting RAB5A through the Ras/Raf/MEK/ERK pathway.

BACKGROUND: Ovarian cancer is one of the most common cancers in women. Profiles changes of microRNAs (miRNAs) are closely linked to malignant tumors. In the present study, we investigated expression of miR-451a in high-grade serous ovarian cancer (HGSOC). We also investigated the potential pathological roles and the likely mechanism of miR-451a in the development of HGSOC using animal models and cell lines. METHODS: Using bioinformatics techniques and a real-time PCR, we analyzed differently expressed miRNAs in HGSOC compared to normal tissue. MTT (i.e. 3-[4, 5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), EDU (i.e. 5-ethynyl-2'-deoxyuridine) and transwell assays were performed to investigate the effect of miR-451a on the proliferation and migration of HGSOC SKOV-3 cells. A dual luciferase reporter assay was performed to verify the targeting relationship of miR-451 and RAB5A (one of the Rab GTPase proteins that regulates endocytosis and vesicle transport). Also, we analyzed levels of the RAB5A mRNA and protein by real-time PCR, western blotting and immunohistochemistry assays in HGSOC cells and tissues. Finally, we performed in vivo experiments using HGSOC mice. RESULTS: miR-451a was substantially upregulated in HGSOC and associated with favorable clinical characteristics. miR-451a knockdown significantly increased growth and metastasis of HGSOC cell line SKOV-3 through Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. In addition, RAB5A, an early endosome marker, was shown to be a direct target of miR-451a. Moreover, RAB5A is correlated with unfavorable clinical features and shows independent prognostic significance in HGSOC. CONCLUSIONS: We found that the miR-451a/RAB5A axis is associated with tumorigenesis and progression through the Ras/Raf/MEK/ERK pathway, providing prognostic indicators and therapeutic targets for patients with HGSOC.

Significant spatial variations of the atmospheric environment at remote site of the Tibetan Plateau - a case study on major ions of precipitation around Nam Co station.

Remote region is normally considered a receptor of long-range transported pollutants. Monitoring stations are important platforms for investigating the atmospheric environment of remote regions. However, the potential contribution of very local sources around these stations may produce important influences on its atmospheric environment, which is still barely studied. In this study, major ions of precipitation were investigated simultaneously at a typical remote station (Nam Co station) and other sites nearby on the Tibetan Plateau (TP) - the so-called "The Third Pole" in the world. The results showed that despite low values compared to those of other remote regions, the concentrations of major ions in precipitation of Nam Co station (e.g., Ca2+: 32.71 µeq/L; [Formula: see text]: 1.73 µeq/L) were significantly higher than those at a site around 2.2 Km away (Ca2+: 11.47 µeq/L; [Formula: see text]: 0.64 µeq/L). This provides direct evidence that atmospheric environment at Nam Co station is significantly influenced by mineral dust and pollutants emitted from surface soil and anthropogenic pollutants of the station itself. Therefore, numbers of other related data reported on the station are influenced. For example, the aerosol concentration and some anthropogenic pollutants reported on Nam Co station should be overestimated. Meanwhile, it is suggested that it is cautious in selecting sites for monitoring the atmospheric environment at the remote station to reduce the potential influence from local sources.

Weak transport of atmospheric water-insoluble particulate carbon from South Asia to the inner Tibetan Plateau in the monsoon season.

Carbonaceous particles play a crucial role in atmospheric radiative forcing. However, our understanding of the behavior and sources of carbonaceous particles in remote regions remains limited. The Tibetan Plateau (TP) is a typical remote region that receives long-range transport of carbonaceous particles from severely polluted areas such as South Asia. Based on carbon isotopic compositions (Δ14C/δ13C) of water-insoluble particulate carbon (IPC) in total suspended particle (TSP), PM2.5, and precipitation samples collected during 2020-22 at the Nam Co Station, a remote site in the inner TP, the following results were achieved: First, fossil fuel contributions (ffossil) to IPC in TSP samples (28.60 ± 9.52 %) were higher than that of precipitation samples (23.11 ± 8.60 %), and it is estimated that the scavenging ratio of IPC from non-fossil fuel sources was around 2 times that from fossil fuel combustion during the monsoon season. The ffossil of IPC in both TSP and PM2.5 samples peaked during the monsoon season. Because heavy precipitation during the monsoon season scavenges large amounts of long-range transported carbonaceous particles, the contribution of local emissions from the TP largely outweighs that from South Asia during this season. The results of the IPC source apportionment based on Δ14C and δ13C in PM2.5 samples showed that the highest contribution of liquid fossil fuel combustion also occurred in the monsoon season, reflecting increased human activities (e.g., tourism) on the TP during this period. The results of this study highlight the longer lifetime of fossil fuel-sourced IPC in the atmosphere than that of non-fossil fuel sources in the inner TP and the importance of local emissions from the TP during the monsoon season. The findings provide new knowledge for model improvement and mitigation of carbonaceous particles.

Disturbance of light-absorbing aerosols on the albedo in a winter snowpack of Central Tibet.

A field observation on the albedo of the snowpack in Central Tibet was conducted in the Nam Co region in the winter of 2011. Snow properties, including grain size and density, were measured in the field, and surface-layer snow samples (down to 5 cm) were collected. The average concentrations of black carbon and dust were 72 ppbm (close to that in the glaciers of Mt. Nyainqentanglha) and 120 ppmm, respectively. Inverse trends were found to exist between the albedo of the snowpack and light-absorbing aerosols (LAAs) as well as grain size growth. Modeling showed that black carbon, dust, and grain growth in the winter snowpack can reduce the broadband albedo by 11%, 28%, and 61%, respectively.

PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway.

PDIA6 have been reported to be involved in a variety of cancers, however, the underlying role in endometrial cancer is still unclear. In this study, we aimed to study the function of PDIA6 in endometrial cancer. Firstly, we verified that PDIA6 was significantly upregulated in endometrial cancer, which was correlated with the progression of endometrial cancer patients. Furthermore, we identified PDIA6 significantly altered the ability of endometrial cancer cells to proliferate and metastasize. In addition, our result illustrated the oncogene effects of PDIA6 in promoting malignant biological behavior of endometrial cancer cells by regulating TGF-ß pathway and being modulated by TRPM2-AS/miR-424-5p axis for the first time. Taken together, this study suggested that PDIA6 may be a new candidate target for endometrial cancer therapy.

SPTBN2 regulated by miR-424-5p promotes endometrial cancer progression via CLDN4/PI3K/AKT axis.

Endometrioid Endometrial Cancer (EEC) is the main subtype of endometrial cancer. In our study, we demonstrated that SPTBN2 was significantly overexpressed in EEC tissues. Upregulated SPTBN2 expression was positively associated with poor prognosis. In addition, we testified that SPTBN2 knockdown significantly inhibited the proliferation, migration, and invasion of EEC cells. Moreover, we found SPTBN2 could interact with CLDN4 to promote endometrial cancer metastasis via PI3K/AKT pathway. Then we further demonstrated that CLDN4 is upregulated in EEC and promotes EEC metastasis. CLDN4 overexpression could partially reversed the decrease in cell migration and invasion caused by SPTBN2 downregulation. In addition, we confirmed that SPTBN2 was a target of miR-424-5p, which plays a tumor suppressor in endometrial cancer. Rescue experiments showed that inhibition of SPTBN2 could partially reverse the effect of miR-424-5p in EEC. In conclusion, we demonstrated that by acting as a significant target of miR-424-5p, SPTBN2 could interact with CLDN4 to promote endometrial cancer metastasis via PI3K/AKT pathway in EEC. Our study revealed the prognostic and metastatic effects of SPTBN2 in EEC, suggesting that SPTBN2 could serve as a prognostic biomarker and a target for metastasis therapy.

EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway.

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

Light absorption and fluorescence characteristics of water-soluble organic compounds in carbonaceous particles at a typical remote site in the southeastern Himalayas and Tibetan Plateau.

Carbonaceous particles play an important role in climate change, and an increase in their emission and deposition causes glacier melting in the Himalayas and the Tibetan Plateau (HTP). This implies that studying their basic characteristics is crucial for a better understanding of the climate forcing observed in this area. Thus, we investigated characteristics of carbonaceous particles at a typical remote site of southeastern HTP. Organic carbon and elemental carbon concentrations at this study site were 1.86 ± 0.84 and 0.18 ± 0.09 µg m-3, respectively, which are much lower than those reported for other frequently monitored stations in the same region. Thus, these values reflect the background characteristics of the study site. Additionally, the absorption coefficient per mass (α/ρ) of water-soluble organic carbon (WSOC) at 365 nm was 0.60 ± 0.19 m2 g-1, with the highest and lowest values corresponding to the winter and monsoon seasons, respectively. Multi-dimensional fluorescence analysis showed that the WSOC consisted of approximately 37% and 63% protein and humic-like components, respectively, and the latter was identified as the component that primarily determined the light absorption ability of the WSOC, which also showed a significant relationship with some major ions, including SO2-4, K+, and Ca2+, indicating that combustion activities as well as mineral dust were two important contributors to WSOC at the study site.

High particulate carbon deposition in Lhasa-a typical city in the Himalayan-Tibetan Plateau due to local contributions.

The Himalayan-Tibetan Plateau is a typical remote region with sparse air pollution. However, air pollution in cites of the inner Himalayan-Tibetan Plateau is relatively serious due to emissions from local residents. Carbonaceous aerosols are not only an important component of air pollutants that affect the health of local residents but also an important trigger of climate change. In this study, the annual wet and dry deposition rates of carbonaceous particles were investigated in Lhasa-a typical city in the Himalayan-Tibetan Plateau, by collecting precipitation and dry deposition samples and analyzing with a thermal-optical measurement protocol. The results showed that the in-situ annual wet deposition rates of water-insoluble organic carbon (WIOC) and black carbon (BC) were 169.6 and 19.4 mg m-2 yr-1, respectively, with the highest and lowest values occurring in the monsoon and non-monsoon periods, respectively. Both precipitation amounts and concentrations of WIOC and BC contributed to wet deposition rates. The dry deposition rates of WIOC and BC in Lhasa had an opposite seasonal variation to that of wet deposition, with annual average deposition rates of 2563.9 and 165.7 mg m-2 yr-1, respectively, which were much higher than those of the nearby glacier region and remote area. These values were also much higher than the results from modeling and empirical calculations, indicating that Lhasa is a high pollution point that cannot capture by models. The results in this study have significant implications for the transport of local emissions in Lhasa to the nearby remote and glacier regions.

The recent deposition of persistent organic pollutants and mercury to the Dasuopu glacier, Mt. Xixiabangma, central Himalayas.

High mountains may serve as condensers for persistent organic pollutants (POPs) and the ice/snow core can provide long-term records of atmospheric deposition of pollutants. In this study, organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in firn core from Dasuopu Glacier were analyzed and the seasonal variation and deposition flux of these pollutants were investigated. PCB 28 was always detected in samples from different firn core layers and concentrations of PCB 28 were in the range of 0.09-0.3 ng/l. Hexachlorobenzene (HCB) and total DDTs (p-p'-DDD and p-p'-DDT) were not always detected and were only present in some samples. No p-p'-DDE and hexachlorocyclohexane (HCH) were detected above the level of determination limits. Concentrations of HCB ranged from 0.04 to 0.07 ng/l, and total DDTs were in the range of 0.15-0.3 ng/l. Total glacier PAHs was below 26 ng/l. The levels of OCPs and PAHs in Dasuopu glacier were roughly similar to values from the European mountain areas but lower than those from Lys glacier (Italy) and glacier from Rocky Mountain. Hg concentration (2-35 ng/l) in firn core samples was higher than that of remote region of Arctic. PCB 28 didn't show obvious variation in different seasons, however for major PAH compounds higher values were observed in summer than in winter. With regard to Hg, it displayed winter maximum. Deposition flux of OCPs, PAHs and mercury showed similar results with maximum flux occurring in the 2000s. After 2000/2001, deposition flux decreased and reflected the possible decrease of emissions of these atmospheric pollutants in the adjacent region.