Enhanced basal autophagy supports ameloblastoma-derived cell survival and reactivation

Sharp, Rachel C.; Effiom, Olajumoke Ajibola; Dhingra, Anuradha; Odukoya, Onatolu; Olawuyi, Adetokunbo Babajide; Arotiba, Godwin Toyin; Boesze‐Battaglia, Kathleen; Akintoye, Sunday O.

doi:10.1016/j.archoralbio.2018.11.013

Cited by 11 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence suggests that lncRNA as a ceRNA regulates OA progression by sponging miRNAs [ 43 , 44 ]. Previously, low HOTAIRM1-1 expression was found to inhibit MSC viability and differentiation via the miR-125b/BMPR2 axis [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis

Chen

Guo

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

Background Growing evidence suggests that long non-coding RNAs (lncRNAs), as decoys of microRNAs (miRNAs), are involved in osteoarthritis (OA) progression, but the potential mechanism of lncRNA SNHG15 in OA remains unknown. Thus, the present study explored the molecular mechanism of SNHG15 in OA progression. Material/Methods OA chondrocytes were created by 20 ng/ml IL-1β stimulation, and the experimental OA model was created by destabilization of the medial meniscus (DMM) surgery. Cartilage histomorphology was observed by safranin and fast green double dyeing. The relationships between SNHG15 and miR-7, KLF4, and miR-7 were determined by dual-luciferase assay or RNA immunoprecipitation (RIP). Immunofluorescence was used to detect the expressions of Ki67, collagen II, and Aggrecan. Moreover, SNHG15, miR-7, KLF4, MMP3, ADAMTS5, COL2A1, Aggrecan, and β-catenin expressions were assessed by qRT-PCR or Western blot. The methylation status of SNHG15 promoter was evaluated by MS-PCR. Results Underexpression of KLF4 and SHNG15 and overexpression of miR-7 were found in human OA knee cartilage tissues and IL-1β-stimulated OA chondrocytes. SHNG15 overexpression significantly inhibited ECM degradation and promoted chondrocyte formation of OA chondrocytes. Furthermore, SNHG15 regulated KLF4 expression by sponging miR-7. Further analysis found that SNHG15 significantly inhibited β-catenin in OA chondrocytes. SNHG15 had a higher level of methylation in human OA tissues than in normal cartilage tissues. Conclusions Our results revealed that SNHG15 alleviated OA progression by regulating ECM homeostasis, which provides a promising target for OA therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis

Chen

Guo

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…Studies have shown that epithelial cells of AB have stronger autophagy activity than mesenchymal cells, human odontogenic cells, and maxillary mesenchymal stem cells, indicating that autophagy may promote the cell viability of residual AB epithelial cells in the hypoxic tumor microenvironment that is in relation to local invasion of AB ( 7 ). Consistently, our data showed that inhibiting autophagy significantly weakened cell proliferation of AM-1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…In the process of tumor development, autophagy may restrain the progression of tumors, but once the tumor is formed, autophagy may facilitate survival and growth of tumor cells (6). A previous study has found that LC-3 and p62 were highly expressed in primary AB-derived epithelial cells (7). Therefore, research on autophagy in odontogenic tumors is of great significance for understanding tumor occurrence and development.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy

et al. 2021

View full text Add to dashboard Cite

Objective: Several clinical trials have suggested that autophagy inhibition is a promising approach for cancer therapy. However, the implications of autophagy in ameloblastoma (AB) remain undiscovered. This study investigated the dysregulated autophagy and its regulatory mechanisms in AB.Methods: The expression and distribution of autophagy-related proteins including B-cell lymphoma-2-interacting protein-1 (Beclin1), microtubule-associated protein 1 light chain 3 (LC3) II/I and lysosomal associated membrane protein 2 (LAMP2) were detected in AB and normal oral mucosa (NOM) tissues by immunohistochemistry and western blot analyses. Under transmission electron microscopy, the autophagy of AB was observed. LAMP2 was a potential target mRNA of miR-1-3p. Quantitative Real-time PCR (qRT-PCR) analysis was utilized for examining LAMP2 and miR-1-3p in AB tissues as well as AM-1 cells. The correlation between LAMP2 and miR-1-3p was analyzed in AB. After transfection with miR-1-3p mimic or inhibitor, LAMP2 expression, proliferation, migration, and invasion were separately detected in AM-1 cells. Rescue assays were finally presented.Results: Our results showed that Beclin1 was lowly expressed as well as LC3II/I and LAMP2 were highly expressed in AB. Autophagosomes were observed in AB. MiR-1-3p was lowly expressed in AB, which exhibited negative correlations to LAMP2 expression. MiR-1-3p up-regulation significantly lowered LAMP2 expression in AM-1 cells. Furthermore, miR-1-3p overexpression restrained proliferative, migrated, and invasive capacities of AM-1 cells, which were ameliorated by LAMP2 overexpression.Conclusion: Our findings demonstrated that miR-1-3p suppressed malignant phenotypes of AB through down-regulating LAMP2-mediated autophagy, which could become an underlying target for AB therapy.

show abstract

“…Autophagic mechanisms may play a role in the behavior of ameloblastomas [6]. Autophagy is a well-coordinated process involving the sequestration of damaged proteins in double-membraned vesicles known as autophagosomes [18].…”

Section: Discussionmentioning

confidence: 99%

“…One study attributed the local invasiveness of ameloblastoma to expression of proteins inducing invadopodia [5]. More recently, Sharp et al inferred that the progression and invasive potential of an ameloblastoma could be associated with the autophagy process [6]. Autophagy is a catabolic process whereby autophagic vesicles sequester injured organelles and proteins for degradation through fusion with the lysosomes [7].…”

Section: Introductionmentioning

confidence: 99%

Immunolocalization of IP3R and V-ATPase in Ameloblastomas

Giovanini

Priesnitz

Til

et al. 2019

Head and Neck Pathol

View full text Add to dashboard Cite

The goal of this study was to investigate the immunolocalization of inositol 1,4,5-trisphosphate receptor (IP3R) and vacuolar ATPase (V-ATPase) in ameloblastomas with special attention to the invasive front. Thirty-seven cases of previously diagnosed formalin-fixed paraffin-embedded (FFPE) human ameloblastoma samples were selected for this study. The samples were grouped according to the predominant histologic pattern and comprised twelve plexiform, eighteen follicular, and seven unicystic ameloblastomas. Of the unicystic variants, six demonstrated purely luminal and intraluminal growth, and one displayed mural extension. One granular cell variant was included in the follicular ameloblastoma group. All specimens were evaluated for IP3R and V-ATPase expression by immunohistochemistry (IHC). IP3R was positive in columnar cells, similar to ameloblasts, and non-peripheral cells in all samples. In the area of tumor protrusion and front of invasion, membranous and cystoplasmic IP3R expression was observed. In contrast, areas adjacent to tumoral protrusion demonstrated only membranous staining patterns. V-ATPase was not expressed in peripheral columnar cells of the unicystic and granular cell variants of ameloblastoma; however, strong staining was present in these cells in plexiform ameloblastomas, follicular ameloblastomas, and areas of mural growth of unicystic ameloblastomas. In areas of tumor protrusion, reactivity for V-ATPase was observed with both membranous and cytoplasmic staining, while other areas showed only membranous V-ATPase. These findings suggest that concomitant immunolocalization of IP3R and V-ATPase, with both cytoplasmic and membranous expression in the peripheral columnar cells, may indicate the invasive potential of ameloblastomas. Furthermore, these results suggest the tumoral spread of ameloblastomas may be correlated with the autophagy process and channelopathy. The expression of these proteins could establish a baseline for future research and provide therapeutic targets for treatment of ameloblastomas.

show abstract

Enhanced basal autophagy supports ameloblastoma-derived cell survival and reactivation

Cited by 11 publications

References 31 publications

Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis

Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis

MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy

Immunolocalization of IP3R and V-ATPase in Ameloblastomas

Contact Info

Product

Resources

About