This investigation was conducted to elucidate whether atractylenolide II could reverse the role of lnc RNA XIST /miR‐30a‐5p/ ROR 1 axis in modulating chemosensitivity of colorectal cancer cells. We totally collected 294 pairs of colorectal cancer tissues and adjacent normal tissues and also purchased colorectal cancer cell lines and human embryonic kidney cell line. 5‐fluorouracil, cisplatin, mitomycin and adriamycin were designated as the chemotherapies for colorectal cell lines, and atractylenolides were arranged as the Chinese drug. The expressions of XIST , miR‐30a‐5p and ROR 1 were quantified with aid of qRT ‐ PCR or Western blot, and luciferase reporter gene assay was implemented to determine the relationships among XIST , miR‐30a‐5p and ROR 1. Our results demonstrated that XIST and ROR 1 expressions were dramatically up‐regulated, yet miR‐30a‐5p expression was down‐regulated within colorectal cancer tissues ( P < 0.05). The overexpressed XIST and ROR 1, as well as under‐expressed miR‐30a‐5p, were inclined to promote viability and proliferation of colorectal cells under the influence of chemo drugs ( P < 0.05). In addition, XIST could directly target miR‐30a‐5p, and ROR 1 acted as the targeted molecule of miR‐30a‐5p. Interestingly, atractylenolides not only switched the expressions of XIST , miR‐30a‐5p and ROR 1 within colorectal cancer cells but also significantly intensified the chemosensitivity of colorectal cancer cells ( P < 0.05). Finally, atractylenolide II was discovered to slow down the viability and proliferation of colorectal cancer cells ( P < 0.05). In conclusion, the XIST /miR‐30a‐5p/ ROR 1 axis could be deemed as pivotal markers underlying colorectal cancer, and administration of atractylenolide II might improve the chemotherapeutic efficacy for colorectal cancer.

Aim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC. Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study. Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells. Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.

Cyanobacteria can utilize CO 2 or even N 2 to produce a variety of high value-added products efficiently. Plastoquinone (PQ) is an important electron carrier in both of the photosynthetic and respiratory electron transport chain. Although the content of PQ, as well as their redox state, have an important effect on physiology and metabolism, there are relatively few studies on the synthesis of PQ and its related metabolic regulation mechanism in photosynthetic microorganisms. In this study, the strategies of overexpression of Geranyl diphosphate: 4-hydroxybenzoate geranyltransferase ( lepgt ) and addition of 4-hydroxybenzoate (4-HB) as the quinone ring precursor were adopted to regulate the biosynthesis of PQ in Synechocystis PCC 6803. Combined with the analysis the photosystem activity, respiration rate and metabolic components, we found the changes of intracellular PQ reprogrammed the metabolism of Synechocystis PCC 6803. The results showed that the overexpression of lepgt reduced PQ content dramatically, by 22.18%. Interestingly, both of the photosynthesis and respiration rate were enhanced. In addition, the intracellular lipid and protein contents were significantly increased. Whereas, the addition of low concentrations of 4-HB enhanced the biosynthesis of PQ, and the intracellular PQ contents were increased by 14.76%–70.86% in different conditions. Addition of 4-HB can regulate the photosystem efficiency and respiration and reprogram the metabolism of Synechocystis PCC 6803 efficiently. In a word, regulating the PQ biosynthesis provided a novel idea for promoting the reprogramming the physiology and metabolism of Synechocystis .

BackgroundBotryococcus braunii is known for its high hydrocarbon content, thus making it a strong candidate feedstock for biofuel production. Previous study has revealed that a high cobalt concentration can promote hydrocarbon synthesis and it has little effect on growth of B. braunii cells. However, mechanisms beyond the cobalt enrichment remain unknown. This study seeks to explore the physiological and transcriptional response and the metabolic pathways involved in cobalt-induced hydrocarbon synthesis in algae cells.ResultsGrowth curves were similar at either normal or high cobalt concentration (4.5 mg/L), suggesting the absence of obvious deleterious effects on growth introduced by cobalt. Photosynthesis indicators (decline in Fv/Fm ratio and chlorophyll content) and reactive oxygen species parameters revealed an increase in physiological stress in the high cobalt concentration. Moreover, cobalt enrichment treatment resulted in higher crude hydrocarbon content (51.3% on day 8) compared with the control (43.4% on day 8) throughout the experiment (with 18.2% improvement finally). Through the de novo assembly and functional annotation of the B. braunii race A SAG 807-1 transcriptome, we retrieved 196,276 non-redundant unigenes with an average length of 1086 bp. Of the assembled unigenes, 89,654 (45.7%), 42,209 (21.5%), and 32,318 (16.5%) were found to be associated with at least one KOG, GO, or KEGG ortholog function. In the early treatment (day 2), the most strongly upregulated genes were those involved in the fatty acid biosynthesis and metabolism and oxidative phosphorylation, whereas the most downregulated genes were those involved in carbohydrate metabolism and photosynthesis. Genes that produce terpenoid liquid hydrocarbons were also well identified and annotated, and 21 (or 29.2%) were differentially expressed along the cobalt treatment.ConclusionsBotryococcus braunii SAG 807-1 can tolerate high cobalt concentration and benefit from hydrocarbon accumulation. The time-course expression profiles for fatty acid biosynthesis, metabolism, and TAG assembly were obtained through different approaches but had equally satisfactory results with the redirection of free long-chain fatty acid and VLCFA away from TAG assembly and oxidation. These molecules served as precursors and backbone supply for the fatty acid-derived hydrocarbon accumulation. These findings provide a foundation for exploiting the regulation mechanisms in B. braunii race A for improved photosynthetic production of hydrocarbons.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1331-5) contains supplementary material, which is available to authorized users.

Microalgae are widely used in the field of food bioengineering. There are relatively few studies on the synthesis of intracellular electron carriers in microalgae and their related metabolic effects. In this study, overexpression of Geranyl diphosphate: 4-hydroxybenzoate geranyltransferase (lepgt), and the addition of 4-hydroxybenzoic acid (4-HB) as quinone ring precursor were adopted to regulate intracellular plastoquinone (PQ) and ubiquinone (UQ) levels in model algae Chlamydomonas reinhardtii. Small changes in PQ and UQ contents could regulate cell growth and metabolism. The expression of lepgt in C. reinhardtii significantly reduced the intracellular contents of PQ and UQ by 49.14% and 98.30%, respectively. The expression of lepgt observably reduced the photosystem activity and respiration rate and increased the contents of neutral lipid and starch by 63.68% and 19.42%, respectively. Exogenous low concentration of 4-HB (1 mM) can effectively improve the contents of intracellular electron carriers, promote respiration, slightly reduce photosystem efficiency, and increase the maximum specific growth rate by 16.93%. It decreased the protein and oil contents by 15.48% and 15.10%, as well as changed the composition of long-chain fatty acids. This paper provided a novel strategy for developing microalgal cell factories for future food production by perturbation on electron carriers of green algae.