Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway.

Objective: Most patients with osteosarcoma (OS) have an extremely poor prognosis. The primary purpose of this investigation was to explore the biological effect of Lnc-CLSTN2-1:1 on OS and the potential processes involved. Materials and procedures: We selected differentially overexpressed Lnc-CLSTN2-1:1 from our laboratory's existing RNA sequence analysis data (fibroblast osteoblast (hFOB 1.19) and three osteosarcoma cell lines (HOS, MG63, and U2OS) as the research object. Next, we detected Lnc-CLSTN2-1:1 in the osteosarcoma HOS cell line and fibroblast cells using qRT-PCR. We evaluated cell proliferation ability using EdU incorporation test, CCK-8 test, and cell clone formation; cell invasion and migration were assessed using the Transwell test, while flow cytometry examined cell cycle, apoptosis, and reactive oxygen species (ROS); Subsequently, the activity changes of selenase (GPx) glutathione peroxidase and (TrxR) thioredoxin reductase were detected. In addition, changes in related proteins were analyzed through Western blotting. Results: The expression of Lnc-CLSTN2-1:1 in osteosarcoma cells was significantly increased. The proliferation, invasion, and migration of osteosarcoma cells were significantly inhibited by knockdown of the expression of Lnc-CLSTN2-1:1, and the cell cycle-related signaling pathway PI3K/AKT/GSK-3ß/cycinD1 was also inhibited. However, insulin-like growth factor-1 (igf-1) could reverse this process. In addition, we examined the activity of two selenophenases (TrxR and GPx) and the changes of ROS before and after Lnc-CLSTN2-1:1 knockdown. The results showed that both TrxR and GPx activities were reduced after Lnc-CLSTN2-1:1 knockdown, resulting in the inhibition of antioxidant stress levels, while intracellular ROS levels were high, which eventually caused killing effects on tumor cells due to the imbalance between oxidative stress and antioxidant stress. Conclusion: Our results showed that Lnc-CLSTN2-1:1 enhanced anti-oxidative stress TrxR and GPx selenoprotein activities through the PI3K/AKT signaling pathway while counteracting the loss of reactive oxygen species ROS produced by mitochondria to osteosarcoma cells, which protected osteosarcoma cells and thus promoted the proliferation and metastatic ability of OS.

Hsa_circ_0087302, a circular RNA, affects the progression of osteosarcoma via the Wnt/ß-catenin signaling pathway.

Osteosarcoma is the most common malignant tumor in adolescent bone malignancies. It has the characteristics of a high metastasis rate, high mortality and poor prognosis. As a subclass of endogenous noncoding RNAs, circRNAs have been identified to be related to the occurrence, development and prognosis of different kinds of cancers, but the mechanism of their effect on osteosarcoma is not clear. In the present study, we identified a novel circRNA, hsa_circ_0087302, by RNA-seq, and we found that it was expressed at low levels in osteosarcoma. Using RT-PCR, we confirmed that the expression of hsa_circ_0087302 in osteosarcoma cells was lower than that in osteoblasts. Functional validation experiments revealed that hsa_circ_0087302 overexpression inhibited proliferation, cell cycle, migration, and invasion in osteosarcoma cells. Furthermore, Western blotting experiments demonstrated that hsa_circ_0087302 affected the expression of cell cycle- and Wnt/ß-catenin signaling pathway-related proteins. For the first time, we identified that hsa_circ_0087302 may affect the malignant biological behavior of osteosarcoma cells through the Wnt/ß-catenin signaling pathway. In summary, hsa_circ_0087302 may provide a new direction for the diagnosis and treatment of osteosarcoma.

A selective control of volatile and non-volatile superconductivity in an insulating copper oxide via ionic liquid gating.

Manipulating the superconducting states of high transition temperature (high-Tc) cuprate superconductors in an efficient and reliable way is of great importance for their applications in next-generation electronics. Here, employing ionic liquid gating, a selective control of volatile and non-volatile superconductivity is achieved in pristine insulating Pr2CuO4±Î´ (PCO) films, based on two distinct mechanisms. Firstly, with positive electric fields, the film can be reversibly switched between superconducting and non-superconducting states, attributed to the carrier doping effect. Secondly, the film becomes more resistive by applying negative bias voltage up to - 4 V, but strikingly, a non-volatile superconductivity is achieved once the gate voltage is removed. Such phenomenon represents a distinctive route of manipulating superconductivity in PCO, resulting from the doping healing of oxygen vacancies in copper-oxygen planes as unravelled by high-resolution scanning transmission electron microscope and in situ X-ray diffraction experiments. The effective manipulation of volatile/non-volatile superconductivity in the same parent cuprate brings more functionalities to superconducting electronics, as well as supplies flexible samples for investigating the nature of quantum phase transitions in high-Tc superconductors.

Ionic Liquid Gating Induced Protonation of Electron-Doped Cuprate Superconductors.

Ion injection controlled by electric field has attracted growing attention due to its tunability over bulk-like materials. Here, we achieve protonation of an electron-doped high-temperature superconductor, La2-xCexCuO4, by gating in the electrochemical regime of the ionic liquid. Such a process induces a superconductor-insulator transition together with the crossing of the Fermi surface reconstruction point. Applying negative voltages not only can reverse the protonation process but also recovers superconductivity in samples deteriorated by moisture in the ambient. Our work extends the application of electric-field-induced protonation into high-temperature cuprate superconductors.