Primary cutaneous anaplastic large-cell lymphoma resembling infratemporal space infection: a case report.

BACKGROUND: Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma belonging to the CD30 + T-cell lymphoproliferative disorders. The case of PC-ALCL in the temporal region is exceedingly rare. Herein, we report a case of PC-ALCL involving the temporal region mimicking infratemporal space infection. CASE PRESENTATION: A 78-year-old woman presented to maxillofacial surgery service with a 6-month history of swelling and pain in the left side of her face. Laboratory investigations found an elevated C-reactive protein (CRP). Imaging findings showed enlarged lymph nodes and extensive thickening of subcutaneous tissue of the left temples. Based on these findings, the infratemporal space infection was suspected initially. The patient underwent incision and drainage, and we unexpectedly found no pus in the lesion area. Incisional biopsy showed necrosis and extensive involvement of the left temples by a diffuse infiltrate containing large, atypical cells. The tumor cells were positive for CD30, CD3, Ki67. They were negative for ALK (SP8), CD5, CD8, CD20 and PAX5. After considering these findings, a diagnosis of PC-ALCL was rendered. The patient was admitted to the lymphoma department for systemic chemotherapy and no relapse occurred during a follow-up period of six months. CONCLUSIONS: This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

Functional significance of O-linked N-acetylglucosamine protein modification in regulating autophagy.

Autophagy is a core molecular pathway that preserves cellular and organismal homeostasis. Being susceptible to nutrient availability and stress, eukaryotic cells recycle or degrade internal components via membrane transport pathways to provide sustainable biological molecules and energy sources. The dysregulation of this highly conserved physiological process has been strongly linked to human disease. Post-translational modification, a mechanism that regulates protein function, plays a crucial role in autophagy regulation. O-linked N-acetylglucosamine protein modification (O-GlcNAcylation), a monosaccharide post-translational modification of intracellular proteins, is essential in nutritional and stress regulatory mechanisms. O-GlcNAcylation has emerged as an essential regulatory mechanism of autophagy. It regulates autophagy throughout its lifetime by targeting the core components of the autophagy regulatory network. This review provides an overview of the O-GlcNAcylation of autophagy-associated proteins and their regulation and function in the autophagy pathway. Therefore, this article may contribute to further understanding of the role of O-GlcNAc-regulated autophagy and provide new perspectives for the treatment of human diseases.

Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy.

The DNA damage response (DDR) safeguards the stable genetic information inheritance by orchestrating a complex protein network in response to DNA damage. However, this mechanism can often hamper the effectiveness of radiotherapy and DNA-damaging chemotherapy in destroying tumor cells, causing cancer resistance. Inhibiting DDR can significantly improve tumor cell sensitivity to radiotherapy and DNA-damaging chemotherapy. Thus, DDR can be a potential target for cancer treatment. Post-translational modifications (PTMs) of DDR-associated proteins profoundly affect their activity and function by covalently attaching new functional groups. O-GlcNAcylation (O-linked-N-acetylglucosaminylation) is an emerging PTM associated with adding and removing O-linked N-acetylglucosamine to serine and threonine residues of proteins. It acts as a dual sensor for nutrients and stress in the cell and is sensitive to DNA damage. However, the explanation behind the specific role of O-GlcNAcylation in the DDR remains remains to be elucidated. To illustrate the complex relationship between O-GlcNAcylation and DDR, this review systematically describes the role of O-GlcNAcylation in DNA repair, cell cycle, and chromatin. We also discuss the defects of current strategies for targeting O-GlcNAcylation-regulated DDR in cancer therapy and suggest potential directions to address them.

The mitochondrial regulation in ferroptosis signaling pathway and its potential strategies for cancer.

Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets.

The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies.

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis and for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed cell death (PCD) is essential in the development of HNSCC as a second messenger. PCD can be categorized into numerous different subroutines: in addition to the two well-known types of apoptosis and autophagy, novel forms of programmed cell death (e.g., necroptosis, pyroptosis, ferroptosis, and NETosis) also serve as key alternatives in tumorigenesis. Cancer cells are not able to avoid all types of cell death simultaneously, since different cell death subroutines follow different regulatory pathways. Herein, we summarize the roles of novel programmed cell death in tumorigenesis and present our interpretations of the molecular mechanisms with a view to the development of further potential therapies.

Expression of YT Domain Family Protein in Oral Squamous Cell Carcinoma and Its Correlation with the Prognosis.

Background: Proteins contained in the conserved YTH521-b homologous (YTH) domain, have m6A-dependent RNA binding activity. As an important part of YTH domain family proteins, YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to reveal the relationship between the expression of these two proteins and the clinical prognosis of OSCC, providing certain guidance for clinical treatment of OSCC. Methods: We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results: We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues. The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusion: Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

Prognostic significance of CircRNAs expression in oral squamous cell carcinoma.

This systematic review was aimed to comprehensively evaluate the clinicopathological and prognostic value of dysregulated expression of circRNAs in OSCC. The research was carried out by searching mainstream electronic databases including PubMed, Embase, Web of Science, Scopus, LILACS, and Cochrane Library to collect relevant studies on prognostic role of circRNAs in OSCC. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, overall survival (OS), disease/recurrence/progression survival (DFS/RFS/PFS), and clinical parameters. This research included 1813 patients from 26 selected articles. The pooled HR values (95% CIs) in OS were 2.38 (1.92-2.93) for oncogenic circRNAs and 0.43 (0.28-0.66) for tumor-suppressor circRNAs, respectively, in DFS/RFS/PFS were 2.34 (1.73-3.17). The meta-analysis on clinicopathology features showed higher level of oncogenic circRNAs is related to advanced TNM stage, tumor stage, worse histological differentiation, positive lymph node and distant metastasis, while enforced expression of tumor-suppressor circRNAs is related to inferior TNM stage, tumor stage and lymphatic metastasis. In conclusion, our meta-analysis implies that circRNAs may be candidate biomarkers for the prognosis and clinicopathology of OSCC.

The microRNA-10b-Bim axis promotes cancer progression through activating autophagy in oral squamous cell carcinoma.

Autophagy is related to many cellular mechanisms and dysregulation of autophagy involves the pathological process in cancer. miR-10b activates autophagy, which promotes invasion and migration of OSCC. Its functional role in the mechanism of OSCC to autophagy remains to be unclear. Overexpression of miR-10b was followed by enhanced OSCC invasion and migration and activated autophagic protein, such as LC3II/ATG5. MiR-10b attracted Bim directly according to the Bio-informatics analyses and double luciferases reporter assays. Functional experiments further revealed that miR-10b could promote invasion and migration in vitro. In addition, miR-10b induced autophagy via inhibiting Bim in invasion and migration of OSCC. Notably, animal experiments confirmed that miR-10b-Bim promoted proliferation and autophagy in OSCC. In addition, this study provides a theoretical support for regulating the mechanism of OSCC by inducing autophagy with miR-10b-Bim as a target.

MiR-152-5p suppresses osteogenic differentiation of mandible mesenchymal stem cells by regulating ATG14-mediated autophagy.

BACKGROUND: Osteoporosis affects the mandible resulting in bone loss. Though impairments are not life threatening, they affect a person's quality-of-life particularly vulnerable elderly. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in regulating bone metabolism. Autophagy is evolutionarily conserved intracellular self-degradation process and is vital in the maintenance of both miRNA and bone homeostasis. However, the role of autophagy in the pathogenesis of miRNA regulating osteoporosis remains unclear. METHODS: In the study, we established a rat osteoporosis model induced by ovariectomy (OVX) and isolated mesenchymal stem cells from mandible (MMSCs-M). Several miRNAs were identified to regulate osteoporosis in some studies. qRT-PCR was applied to examine the expression of miRNA, autophagy and osteogenic differentiation-related genes. Western blotting assays were performed to detect the expression of autophagy and osteogenic differentiation proteins. Immunofluorescence and transmission electron microscope were used to verify the autophagy activity. Transfecting technology was used to enhance or suppress the expression of miR-152-5p which enable us to observe the relationship between miR-152-5p, autophagy and osteogenic differentiation. Additionally, the measurement of reactive oxygen species was used to investigate the mechanism of autophagy affecting osteogenic differentiation. RESULTS: We found an upregulated expression of miR-152-5p in MMSCs-M in OVX group. Downregulated autophagy-related gene, proteins and autophagosome were detected in vitro of OVX group compared with sham group. Moreover, downregulation of miR-152-5p promoted osteogenic differentiation of MMSCs-M as well as enhanced autophagy-related proteins in OVX group. Conversely, overexpression of miR-152-5p showed opposite effect in sham group. Meanwhile, we found Atg14 (autophagy-related protein homolog 14) was identified to be a direct target of miR-152-5p theoretically and functionally. In other words, we confirmed inhibition of miR-152-5p promoted the osteogenic differentiation via promoting ATG14-mediated autophagy. Furthermore, miR-152-5p/ATG14-mediated autophagy regulated osteogenic differentiation by reducing the endogenous ROS accumulation and maintaining cellular redox homeostasis. CONCLUSION: Our data suggest that miR-152-5p is the first identified to regulate osteogenic differentiation by directly targeting autophagy-related protein ATG14 and regulating oxidative stress and therapeutic inhibition of miR-152-5p may be an efficient anabolic strategy for osteoporosis.

Potential applications of N6 -methyladenosine modification in the prognosis and treatment of cancers via modulating apoptosis, autophagy, and ferroptosis.

N6 -methyladenosine (m6 A) is one of the most abundant modifications determining the fate of RNA. Currently, m6 A modification is tightly connected with tumorigenesis and presents novel promise in clinical applications. Regulated cell death (RCD) is a programmed mechanism that plays a complicated role in malignant transition. Regarding the main forms of RCD, aberrant levels of m6 A modification have been detected during the progression of apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis in several diseases. However, few reviews have elucidated the correlation between m6 A-modified RCD and carcinogenesis. In this review, we summarize the regulators of m6 A methylation and their functions in carcinogenesis through an overview of m6 A-modified RCD. Additionally, we assume the potential role of m6 A modification regulators as novel biomarkers for chemotherapies and precision medicine. Furthermore, we review the controversies and conflicts in m6 A explorations and predict future orientations of m6 A-modified RCD for clinical applications. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas.

Autophagy is an evolutionally conserved catabolic process that degrades cells to maintain homeostasis. Cisplatin-activated autophagy promotes the expression of circ-PKD2, which plays a role as a tumor suppressor gene in the proliferation, migration, and invasion in oral squamous cell carcinoma (OSCC). However, the role of circ-PKD2 in regulating the sensitivity of OSCC patients to cisplatin remains to be elucidated. Overexpression of circ-PKD2 increased the formation of autophagosomes in OSCC cells and activation of proteins, such as LC3 II/I. Its activation effect on autophagy was, however, alleviated by 3-MA. Bioinformatics analyses and double luciferases reporter assays conducted in this study confirmed the existence of targeted relationships between circ-PKD2 and miR-646 and miR-646 and Atg13. Functional experiments further revealed that miR-646 reversed the autophagy and apoptosis effects of circ-PKD2 in OSCC cells treated with cisplatin. In addition, circ-PKD2 promoted the expression of ATG13 by adsorption of miR-646. Its interference with Atg13 alleviated the activation effects of circ-PKD2 on autophagy and apoptosis of miR-646. Notably, the in vivo animal experiments also confirmed that circ-PKD2 inhibited tumor proliferation and activated autophagy in OSCC cells. This study provides a theoretical basis for using circ-PKD2 as a target to regulate the sensitivity of OSCC patients to cisplatin, thus increasing its chemotherapeutic effects.

MiR-34c-3p upregulates erastin-induced ferroptosis to inhibit proliferation in oral squamous cell carcinomas by targeting SLC7A11.

BACKGROUND: MiRNA is a small molecule RNA that plays an important role in a variety of physiological and pathological processes., and miR-34c-3p has been demonstrated to be closely related to the occurrence of tumors. Ferroptosis is a new form of cell death characterized by lipid-based reactive oxygen species accumulation. However, it is still unclear how miR-34c-3p influences the development of oral squamous cell carcinoma (OSCC) by regulating ferroptosis. Therefore, the main objective of this study was to explore the role and mechanism of miR-34c-3p in OSCC. MATERIALS AND METHODS: The expression of miR-34c-3p in OSCC and matched normal tissues was detected by quantitative real-time PCR (qRT-PCR). Subsequently, the effect of miR-34c-3p overexpression on cell proliferation and ferroptosis was evaluated using CCK8, colony formation assays, Live/Dead staining, Western blotting analysis, ROS, MDA, and GSH assay. RESULTS: The results showed lower expression of miR-34c-3p in OSSC compared with normal tissues. Overexpression of miR-34c-3p in SCC-25 cells suppressed cell proliferation. In addition, the overexpression of miR-34c-3p promoted ferroptosis by increasing ROS, MDA, and iron and decreasing GSH and GPX4 levels in SCC-25 cells. CONCLUSION: Our findings revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC through the miR-34c-3p/SLC7A11 axis, suggesting new insights into OSCC and a potentially useful therapeutic strategy for OSCC.

Upregulation of mmu_circ_0001066 attenuates the inhibitory effect of bisphosphonates on osteoclastogenesis.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is the main adverse side effect of bisphosphonates (BPs), mainly owing to the inhibitory effect of BPs on osteoclastogenesis. CircRNAs were identified to be an important factor in regulating cellular processes. The aim of this study was to explore the effect of mmu_circ_0001066 on BP-inhibited osteoclastogenesis. MATERIALS AND METHODS: The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Bioinformatics techniques were applied to screen potential circRNAs. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were used to examine the effect of mmu_circ_0001066 on osteoclastogenesis. Bioinformatics analysis, luciferase reporter assays, and Western blotting assays were performed to investigate the underlying mechanism. RESULTS: Four MRONJ-related miRNAs were upregulated in BP-treated RAW264.7 cells, and the expression of mmu_circ_0001066 was negatively correlated with those of MRONJ-related miRNAs. Furthermore, the upregulation of mmu_circ_0001066 partially attenuated the inhibitory effect of BP on osteoclastogenesis in RAW264.7 cells. Mechanistically, upregulated miR-16 suppressed osteoclastogenesis and miR-16 inhibitor increased osteoclastogenesis. Furthermore, we have identified that miR-16 is a downstream effector of mmu_circ_0001066. CONCLUSION: Our results suggest that mmu_circ_0001066 played an important role in the BP-mediated suppression of osteoclastogenesis, which lays a foundation for identifying mmu_circ_0001066 as a potential biomarker for MRONJ.