NPHS2-6 drives cervical squamous cell carcinoma (CSCC) progression via hsa-miR-1323/SMC1B axis to activate PI3K-Akt pathway

Purpose A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. Methods The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. Results NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. Conclusions In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC (AU)

NPHS2-6 drives cervical squamous cell carcinoma (CSCC) progression via hsa-miR-1323/SMC1B axis to activate PI3K-Akt pathway.

PURPOSE: A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. METHODS: The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. RESULTS: NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. CONCLUSIONS: In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC.

New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma.

BACKGROUND: N6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC. METHODS: We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP. RESULTS: METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A "reader" YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2. CONCLUSIONS: In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.

High-light inhibition of two submerged macrophytes in a shallow water experiment.

The negative effects, caused by high light, on algae, terrestrial and marine aquatic plants are well documented; those negative effects on freshwater submerged plants are, however, not well known. We determined the negative effects of two common submerged species, Myriophyllum spicatum and Vallisneria natans, on their growth and reproduction in a shallow water experiment along an irradiance gradient. Our results highlighted that the plant mass, relative growth rate and shoot height of V. natans and M. spicatum, and root mass and root length:root mass of M. spicatum and leaf mass and shoot height:shoot mass of V. natans were significantly negatively affected in shallow water with high-light regime (>50 % of full light). While the ramet number of the two species was stimulated by from 20.0 to 36.4 %, and root length, root:shoot, chlorophyll (a:b), chlorophyll (a + b), leaf carbon, nitrogen and phosphorus contents of the two studied macrophytes were not significantly impacted by light. Our results indicated that the high-light inhibition of plant growth was greater on the shoots than on the roots of the plants, although these effects were significantly different between the two studied submerged species and among the measured traits. Accordingly, we should avoid negative effects caused by high light to improve the performance of submerged species when we conduct submerged aquatic vegetation restoration programmes in eutrophic lakes.

Trends and Health Risks of Dissolved Heavy Metal Pollution in Global River and Lake Water from 1970 to 2017.

Heavy metal pollution in surface water is a global environmental problem. This study analyzed the trends, health risks, and sources of eight dissolved heavy metal species in river and lake water across five continents (Africa, Asia, Europe, North America, and South America; Oceania was excluded owing to a lack of data) for the period 1970-2017. We wanted to assess the effects of various implemented countermeasures to pollution and to determine those that could be adopted worldwide. Collectively, the water system showed increasing trends for Cd, Cr, Cu, Ni, Mn, and Fe and decreasing trends for Pb and Zn. The mean dissolved concentrations of most heavy metals were highest in Asia and lowest in Europe. Most heavy metals had low non-carcinogenic risks over this period. The cancer risks associated with Pb were lower than the hazardous level on all five continents over the five decades, whereas the cancer risks related to Cr exceeded the hazardous level in the 1970s, 2000s, and 2010s, and in Africa, Asia, and North America over the entire period. Mining and manufacturing were consistently found to be critical sources of metal pollution from 1970 to 2017. However, the heavy metal sources differed significantly by continent, with waste discharge and rock weathering dominant in Africa; mining and manufacturing, along with rock weathering, are dominant in Asia and South America; fertilizer and pesticide use, along with rock weathering, are dominant in North America; and mining and manufacturing, waste discharge, and rock weathering are dominant in Europe. Global trends in the metal loadings in water and in relevant pollution-control measures suggest that countermeasures in Europe have successfully controlled heavy metal pollution. The successful measures include implementing rigorous standards for metal emissions, limiting the metal concentrations in products, and rigorously treating metal-contaminated waste. Therefore, the measures implemented in Europe should be extended worldwide to treat heavy metal pollution in water.

The factors affecting a native obligate parasite, Cuscuta australis, in selecting an exotic weed, Humulus scandens, as its host.

In weed management, using native parasites to control exotic weeds is considered a better alternative than classical biological control. But the risk must be assessed because of the potential damage caused by these agents. We conducted this project to investigate the mechanism driving the choice of a native obligate parasite, Cuscuta australis, between the exotic, Humulus scandens, and native plants as its host through field and pot experiments. The results showed that C. australis preferred the exotic weed over native (naturalized) hosts and caused a notable reduction in the biomass of H. scandens in the field. In contrast, the results of the pot experimentindicated that C. australis preferred a mix of native (naturalized) hosts over the exotic weed. Both texperiments indicated that the parasitic preference of C. australis was induced more by light irradiance than plant water, carbon (C), nitrogen (N) and phosphorus (P) contents, indicating that the native parasite can only be used to control H. scandens when the exotic weed forms mono-cultures or dominates the community. Accordingly, induction and release of C. australis to control H. scandens should be conducted with great caution.