Although underexpression of miR-9 in cancer cells is reported in many cancer types, it is currently difficult to classify miR-9 as a tumor suppressor or an oncomir. We demonstrate that miR-9 expression is down-regulated in MCF-7 and MDA-MB-231 breast cancer cells compared with MCF-10-2A normal breast cell line. Increasing miR-9 expression levels in breast cancer cells induced anti-proliferative, anti-invasive, and pro-apoptotic activity. In addition, microarray profiling of the transcriptome of MCF-7 cells overexpressing miR-9 identified six novel direct miR-9 targets (AP3B1, CCNG1, LARP1, MTHFD1L, MTHFD2, and SRPK1). Among these, MTHFD2 was identified as a miR-9 target gene that affects cell proliferation. Knockdown of MTHFD2 mimicked the effect observed when miR-9 was overexpressed by decreasing cell viability and increasing apoptotic activity. Despite variable effects on different cell lines, proliferative and anti-apoptotic activity of MTHFD2 was demonstrated whereby it could escape from miR-9-directed suppression (by overexpression of MTHFD2 with mutated miR-9 binding sites). Furthermore, endogenous expression levels of miR-9 and MTHFD2 displayed inverse expression profiles in primary breast tumor samples compared with normal breast samples; miR-9 was down-regulated, and MTHFD2 was up-regulated. These results indicate anti-proliferative and pro-apoptotic activity of miR-9 and that direct targeting of MTHFD2 can contribute to tumor suppressor-like activity of miR-9 in breast cancer cells.

Cyanobacteria are one of the earliest branching groups of organisms on the planet, and during their evolutionary history were submitted to varying selective pressures. Nowadays, cyanobacteria can grow in a variety of conditions, using a large number of nitrogen sources. The control of the nitrogen metabolism in cyanobacteria depends on a fine-tuning regulatory network involving 2-oxoglutarate (2-OG), PII, PipX, and NtcA. This network answers to the cellular 2-OG levels, which reflects the cellular carbon/nitrogen balance, and as an output regulates gene expression, translation, protein activities and thus metabolic pathways. Hence, the diurnal regulation of growth may be directly dependent of this network, as it coordinates the use of photoassimilates towards either growth or the accumulation of reserves, based on the environmental conditions. Therefore, analysis of the nitrogen control network is not only important to comprehend the metabolic control of growth in cyanobacteria, but is also a target to improve cyanobacterial biotechnological potential. In this review, we discuss the mechanisms involved in the control of nitrogen metabolism and its potential role in the diurnal regulation of growth. Then, we highlight why a better understanding of the mechanisms involved in the partitioning of carbon and nitrogen towards growth or storage would increase the biotechnological potential of these organisms.

Green tides, the phenomenon whereby large volume of marine environment is taken over by the sea lettuce Ulva spp, are a seasonal occurrence thought to be caused mainly by anthropogenic eutrophication. The aggravation of green tide occurrence since the 1970s could however be due to the amplification of fast-growing strains within these areas. In this study, we compared the growth and metabolite content of 28 green tide Ulva strains against 100 non-green tide strains, under conditions close to those encountered in green tides areas. The aim was to determine whether the presence of specific characteristics intrinsic to green tide strains could in itself be a major factor for their reoccurrence. We confirmed that green tide strains have specific characteristics, with faster tissue expansion, higher protein and pigments, and lower starch content compared to non-green tide ones, thus highlighting a genetic component specific to green tide strains. Dry biomass accumulation, however, was not different between the two types of Ulva strains. Hence, we hypothesise that the selective pressure in green tide areas leads to the amplification of Ulva genotypes best adapted for this environment. Such selection of fast-growing strains would indicate that green tides are likely to become more prevalent and of higher magnitude over the coming years.

Green macroalgae of the genus Ulva play a key role in coastal ecosystems and are of increasing commercial importance. However, physiological differences between strains and species have yet to be described in detail. Furthermore, the strains of Ulva used in aquaculture usually originate from opportunistic collection in the wild without prior selection of best performing strains. Hence, efforts are required to detect the potential variability in growth and metabolic accumulation between Ulva strains and ultimately select the best performing strains under given environmental conditions. Here, the growth, physiological, and metabolic characteristics of 49 laminar Ulva spp. strains were investigated using a custom-made high-throughput phenotyping platform, enzymatic assays, and gas chromatography-mass spectrometry. We found large natural variation for a wide range of growth and metabolic characteristics, with growth rates varying from 0.09 to 0.37 mg.mg⁻¹.d⁻¹ among strains. Ulva spp. possess a unique diurnal growth pattern and primary metabolism compared with land plants, with higher growth rates during the night than during the light period. Starch and sucrose only contributed on average 35% of the carbon required to sustain Ulva’s night growth. Nitrates accumulated during the night in Ulva tissues, and nitrate accumulation and consumption was positively correlated with growth. In addition, we identified six amino acids as possible biomarkers for high growth in Ulva. The large variability in growth and metabolite accumulation recorded among morphologically similar Ulva strains justifies future efforts in strain selection for increasing biomass, metabolite yields, and nutrient removal in the growing aquaculture industry.