CircPCNXL2 promotes papillary thyroid carcinoma progression by regulating fatty acid metabolism induced by anabolic enzyme ACC1.

Papillary thyroid cancer (PTC) is an endocrine malignant tumor with a rapidly increasing incidence in recent years. Although the disease prognosis is good in general, there are still some patients with local invasion, distant metastasis and recurrence, which make treatment difficult. This study aimed to investigate the effect of a novel circRNA, circPCNXL2, on the progression of PTC and to explore its underlying mechanism in PTC. In this study, we found that the expression of circPCNXL2 was upregulated in PTC, which was positively correlated with the proliferation of PTC, and knockdown of circPCNXL2 enhanced the cell cycle arrest of PTC and promoted cell apoptosis. Further research revealed that circPCNXL2 can interact with ACC1, a key enzyme of cellular lipid metabolism, and then promote cell growth by affecting the de novo synthesis of fatty acids. Mechanistically, circPCNXL2 enhances the protein activity of ACC1 by reducing ACC1 phosphorylation of ser79, thereby promoting the formation of fatty acids such as free fatty acids and triglycerides in cells to meet the energy metabolism needs of cells and promote cell growth. In a nude mouse subcutaneous tumorigenesis model, knockdown of circPCNXL2 inhibited the growth of PTC tumors. This study revealed that circPCNXL2 regulates PTC lipid metabolism by enhancing the protein activity of ACC1 and identified a novel signaling pathway, the circPCNXL2-ACC1 axis, that can be targeted for the treatment of PTC.

Gasless submental-transoral combined approach endoscopic thyroidectomy: a new surgical technique.

Background: The development of transoral endoscopic vestibular approach thyroidectomy (TOETVA) has been limited by inherent defects, such as mental nerve injury and carbon dioxide (CO2)-related complications. Herein, we proposed a new technique without CO2 called gasless submental-transoral combined approach endoscopic thyroidectomy (STET) to solve the problems in TOETVA. Methods: We reviewed 75 patients who successfully underwent gasless STET using novel instruments at our institution from November 2020 to November 2021. A main incision of approximately 2 cm was made in the natural submental crease line and then combined with two vestibule incisions to complete the procedure. Demographic data, surgical technique and perioperative outcomes were retrospectively recorded. Results: Thirteen male and sixty-two female patients with a mean age of 34.0 ± 8.1 years were enrolled in this study. Sixty-eight patients had papillary thyroid carcinomas and seven had benign nodules. We successfully performed all gasless STET without conversion to open surgery. The average postoperative hospital stay was 4.2 ± 1.8 days. One transient recurrent laryngeal nerve injury and two transient hypoparathyroidisms were observed. Three patients complained of slight lower lip numbness on the first postoperative day. One case of lymphatic fistula, subcutaneous effusion, and incision swelling occurred each, all of which were conservatively cured. One patient developed a recurrence six months after surgery. Conclusions: Gasless STET using our own designed suspension system is technically safe and feasible with reasonable operative and oncologic results.

Novel suspension system for gasless transoral vestibular thyroidectomy.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is receiving increased attention, frequently due to growing requirements for cosmetic incisions. Here, we report our initial experience and discuss the safety and efficacy of the innovative surgical working space suspension system for gasless TOETVA. METHODS: We retrospectively analyzed 75 consecutive patients for whom gasless TOETVA with our novel working space suspension system was used. This suspension system included self-developed retractors, a sterile bandage, and an anesthesia stand. We also improved some main surgical instruments in gasless TOETVA. RESULTS: The study included 75 patients who successfully underwent thyroidectomy and central neck dissection via gasless TOETVA. The mean operating time was 143.27 ± 34.60 min. The mean number of retrieved lymph nodes was 8.00 ± 5.39. Conversion to open surgery did not occur, nor did patients exhibit serious postoperative complications. Postoperative complications included 4 cases of transient recurrent laryngeal nerve (RLN) palsy, 9 of transient hypoparathyroidism, and 3 of transient mental nerve injury. One patient with subcutaneous fluid after surgery recovered after aspiration. Another patient with submental minor perforation recovered well after suturing. There was no evidence of specific complications related to self-designed retractors. CONCLUSION: The innovative working space suspension system for gasless TOETVA provided enough and stable working space and optimized the clarity of the surgical field without CO2-related complications.

Oxidative stress-induced circKIF18A downregulation impairs MCM7-mediated anti-senescence in intervertebral disc degeneration.

Low back pain, triggered by intervertebral disc degeneration (IVDD), is one of the most common causes of disability and financial expenditure worldwide. However, except for surgical interventions, effective medical treatment to prevent the progression of IVDD is lacking. This study aimed to investigate the effects of circKIF18A, a novel circRNA, on IVDD progression and to explore its underlying mechanism in IVDD. In this study, we found that oxidative stress was positively correlated with nucleus pulposus cell (NPC) senescence in IVDD and that circKIF18A was downregulated in IVDD and attenuated senescent phenotypes such as cell cycle arrest and extracellular matrix degradation in NPCs. Mechanistically, circKIF18A competitively suppressed ubiquitin-mediated proteasomal degradation of MCM7, and the protective effects of circKIF18A on NPCs were partially mediated by MCM7 under oxidative stress. Intradiscal injection of adenoviral circKIF18A ameliorated IVDD in a rat model. This study revealed that circKIF18A regulates NPC degeneration by stabilizing MCM7 and identified a novel signaling pathway, the circKIF18A-MCM7 axis, for anti-senescence molecular therapy in IVDD.

CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway.

Papillary thyroid cancer (PTC) is a common endocrine tumor with a rapidly increasing incidence in recent years. Although the majority of PTCs are relatively indolent and have a good prognosis, a certain proportion is highly aggressive with lymphatic metastasis, iodine resistance, and easy recurrence. Circular RNAs (circRNAs) are a class of noncoding RNAs that are linked to a variety of tumor processes in several cancers, including PTC. In the current study, circRNA high-throughput sequencing was performed to identify alterations in circRNA expression levels in PTC tissues. circTIAM1 was then selected because of its increased expression in PTC and association with apoptosis, proliferation, and migration of PTC cells in vitro and in vivo. Mechanistically, circTIAM1 acted as a sponge of microRNA-646 and functioned in PTC by targeting miR-646 and heterogeneous ribonucleoprotein A1. Fluorescence in situ hybridization and dual-luciferase reporter assays further confirmed these connections. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and may represent a potentially therapeutic target against PTC progression.

circCAMSAP1 promotes osteosarcoma progression and metastasis by sponging miR-145-5p and regulating FLI1 expression.

Osteosarcoma is the most common primary malignant bone tumor in adolescents. While chemotherapy combined with surgery can improve the prognosis of some patients, chemo-resistance is still a huge obstacle in osteosarcoma treatment. Accumulating evidence demonstrates that circular RNAs (circRNAs) are involved in cancer progression and metastasis, but their specific role in osteosarcoma remains mostly undescribed. In this study, we performed circRNA deep sequencing and identified 88 distinct circRNAs from a human osteosarcoma cell lines group (143B, HOS, SJSA, and U2OS) and the human osteoblast hFOB 1.19 (control). We found that circCAMSAP1, also named hsa_circ_0004338, is significantly upregulated in human osteosarcoma tissues and cell lines, and it is positively correlated with osteosarcoma development. Silencing of circCAMSAP1 effectively suppresses osteosarcoma cell growth, apoptosis, migration, and invasion. Furthermore, we validated that circCAMSAP1 functions in osteosarcoma tumorigenesis through a circCAMSAP1/miR-145-5p/friend leukemia virus integration 1 (FLI1) pathway. FLI1 promotes osteosarcoma tumorigenesis and miR-145-5p suppresses FLI translation. circCAMSAP1 directly sequesters miR-145-5p in the cytoplasm and inhibits its activity to suppress osteosarcoma tumorigenesis. Moreover, the regulatory role of circCAMSAP1 upregulation was examined and validated in rats. In summary, our findings provide evidence that circCAMSAP1 act as a "microRNA sponge" and suggest a new therapeutic target of human osteosarcoma.

Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression.

Papillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.

Sanguinarine protects against ovariectomy­induced osteoporosis in mice.

Natural compounds are alternative agents that have therapeutic potential for preventing and treating osteoporosis. Traditionally, sanguinarine has been used clinically due to its diverse biological properties, including antimicrobial, anti­inflammatory and anticancer effects. Recently, for the first time, it was reported that sanguinarine inhibits osteoclast differentiation and bone resorption by suppressing the tumor necrosis factor ligand superfamily member 11­induced nuclear factor­κB and extracellular signal­regulated kinase signaling pathways in vitro. Therefore, the present study further investigated the pharmacological effect of sanguinarine on osteoporosis in vivo. Micro­computed tomography and histomorphometry analysis demonstrated that sanguinarine, at low and high concentrations, prevents ovariectomy (OVX)­induced bone loss. In addition, further investigation of the cellular response in vivo revealed that sanguinarine inhibited osteoclastic bone resorption and promoted osteoblastic bone formation in a dose­dependent manner. Therefore, the present study demonstrated that sanguinarine protected mice from OVX­induced osteoporosis by modulating bone remodeling, indicating that sanguinarine may have potential in the treatment of osteoporosis.

Validation of downregulated microRNAs during osteoclast formation and osteoporosis progression.

Enhanced osteoclast formation and function have essential roles during post­menopausal osteoporosis. A number of cytokines have been reported to regulate osteoclastogenesis and to be involved during the pathogenesis of osteoporosis. However, the regulation of osteolysis by microRNAs (miRNAs) has remained to be fully elucidated. The present study used a microarray analysis to identify a variety of miRNAs that are differentially expressed during osteoclast formation. Six down­regulated miRNAs, miR­21a­5p, miR­27a­3p, let­7i­5p, miR­22­3p, miR­340­5p and miR­23a­5p, whose molecular mechanisms during osteoclast differentiation have not been reported previously, were further assessed. Using an osteoclast formation assay and a mouse model of progressive osteoporosis, the downregulation of these miRNAs was validated in vitro and in vivo. Of note, the expression patterns of these six miRNAs were associated with the progression of osteoporosis. Therefore, these miRNAs are of potential diagnostic and therapeutic value for osteolytic diseases.