Objective. Hsa_circ_0001955 presents significant upregulation in colorectal cancer (CRC) tissues. However, its role in CRC remains unclear. Thus, we attempted to clarify functions of hsa_circ_0001955 on CRC. Methods. qRT-PCR was performed to examine hsa_circ_0001955, miR-583, and FGF21 levels. Western blotting was conducted to measure FGF21 protein expression. CCK-8, flow cytometry, and Ki-67 immunohistochemical staining and TUNEL assays were conducted to assess proliferation and apoptosis in vitro and in vivo, respectively. Cell invasion and migration were assessed by Transwell assay. Tumor-bearing mouse model and HE staining were used to assess inflammatory injury. Luciferase reporter system and RNA pull-down were conducted to evaluate the regulation between miR-583 and hsa_circ_0001955 or FGF21. Results. We found that hsa_circ_0001955 showed characteristics of upregulated circRNA in CRC. Further analysis indicated that hsa_circ_0001955 elevation facilitated CRC cell malignancy in vitro and promoted tumor growth in vivo. Furthermore, hsa_circ_0001955 was a miR-583 sponge and FGF21 was directly targeted by miR-583. In addition, we found that downregulation of miR-583 promoted hsa_circ_0001955-mediated CRC cell malignancy in vitro. In contrast, FGF21 elevation promoted miR-583-regulated CRC cell malignancy in vitro. Conclusion. We demonstrated that hsa_circ_0001955 facilitated CRC progression via miR-583/FGF21 axis, suggesting that hsa_circ_0001955 may provide a novel insight for therapy of CRC.

Our previous work revealed mutual and specific metabolites/pathways in artemisinin‐sensitive and ‐resistant Plasmodium berghei K173‐infected mice. In this study, we further investigated whether chrysosplenetin, a candidate chemical to prevent artemisinin resistance, can regulate these metabolites/pathways by integrating nontargeted metabolomics with 1H NMR and LC–Q‐TOF–MS/MS spectrum. The nuclear magnetic resonance method generated specifically altered metabolites in response to co‐treatment with chrysosplenetin, including: the products of glycolysis such as glucose, pyruvate, lactate and alanine; taurine, closely associated with liver injury; arginine and proline as essential amino acids for parasites; TMAO, a biomarker for dysbacteriosis and renal function; and tyrosine, which is used to generate levodopa and dopamine and may improve the torpor state of mice. Importantly, we noticed that chrysosplenetin might depress the activated glycolysis induced by sensitive parasites, but oppositely promoted the inhibited glycolysis to generate more lactate, which suppresses the proliferation of resistant parasites. Moreover, chrysosplentin possibly disturbs the heme biosynthetic pathway in mitochondria. The MS method yielded changed coenzyme A, phosphatidylcholine and ceramides, closely related to mitochondria β‐oxidation, cell proliferation, differentiation and apoptosis. These two means shared no overlapped metabolites and formed a more broader metabolic map to study the potential mechanisms of chrysosplenetin as a promising artemisinin resistance inhibitor.

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