Ubiquitin-Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma.

Tumor-derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin-specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell-derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell-derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.

USP22 is required for human endometrial stromal cell proliferation and decidualization by deubiquitinating FoxM1.

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.

Ubiquitin-specific protease 22 promotes tumorigenesis and progression by an FKBP12/mTORC1/autophagy positive feedback loop in hepatocellular carcinoma.

Ubiquitin-specific protease 22 (USP22) has been identified as a potential marker for cancer stem cells in hepatocellular carcinoma (HCC). It can promote HCC stemness, which is considered a driver of tumorigenesis. Here, we sought to determine the role of USP22 in tumorigenesis, elucidate its underlying mechanism, and explore its therapeutic significance in HCC. As a result, we found that tissue-specific Usp22 overexpression accelerated tumorigenesis, whereas Usp22 ablation decelerated it in a c-Myc/NRasGV12-induced HCC mouse model and that the mammalian target of rapamycin complex 1 (mTORC1) pathway was activated downstream. USP22 overexpression resulted in increased tumorigenic properties that were reversed by rapamycin in vitro and in vivo. In addition, USP22 activated mTORC1 by deubiquitinating FK506-binding protein 12 (FKBP12) and activated mTORC1, in turn, further stabilizing USP22 by inhibiting autophagic degradation. Clinically, HCC patients with high USP22 expression tend to benefit from mTOR inhibitors after liver transplantation (LT). Our results revealed that USP22 promoted tumorigenesis and progression via an FKBP12/mTORC1/autophagy positive feedback loop in HCC. Clinically, USP22 may be an effective biomarker for selecting eligible recipients with HCC for anti-mTOR-based therapy after LT.

A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function.

BACKGROUND: The study aims to explore the role of A1BG antisense RNA 1 (A1BG-AS1), microRNA (miR)-148a-3p and ubiquitin-specific protease 22 (USP22) on osteosarcoma (OS) cell growth. RESEARCH DESIGN & METHODS: A1BG-AS1, miR-148a-3p, USP22, and silent information regulator 2 homolog 1 (SIRT1) levels in OS tissues and cells were determined. The effects of A1BG-AS1, miR-148a-3p, and USP22 on the biological functions of OS cells were examined by functional assays. In vivo assay was conducted to observe the effect of A1BG-AS1 on OS growth in vitro. The relationship of A1BG-AS1, miR-148a-3p, and USP22 was analyzed by bioinformatics analysis, RNA-fluorescence in situ hybridization, luciferase activity, and RNA binding protein immunoprecipitation assays. The relation between USP22 and SIRT1 was evaluated by immunoprecipitation. RESULTS: A1BG-AS1 and USP22 were highly expressed, and miR-148a-3p was lowly expressed in OS tissues and cells. Down-regulation of A1BG-AS1 and USP22 or up-regulation of miR-148a-3p impaired the malignant behaviors of OS cells. A1BG-AS1 sponged miR-148a-3p, and miR-148a-3p targeted USP22, thereby inhibiting USP22 expression. Up-regulating USP22 reversed the A1BG-AS1 suppression-induced phenotypic inhibition of OS cells. USP22 affected the biological functions of OS cells by deubiquitinating SIRT1. CONCLUSION: A1BG-AS1 facilitates the biological functions of OS cells via mediating the miR-148a-3p/USP22 axis.

Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications.

Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to participate in the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study, herein, aimed to identify the functional significance and machinery of miR-30d in the progression of thyroid cancer. MiR-30b presented aberrant low expression and ubiquitin-specific protease 22 (USP22) exhibited aberrant high expression in thyroid cancer tissues and cells. The current study proposed the possible machinery that miR-30d could target and negatively regulate USP22. Additionally, USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. Responding to the gain- or loss-of-function of miR-30d and/or USP22, behaviors of thyroid cancer cells were altered. Accordingly, miR-30d inhibited proliferation and promoted apoptosis of thyroid cancer cells by suppressing USP22 through SIRT1/FOXO3a/PUMA axis. The effects of miR-30d and USP22-mediated SIRT1/FOXO3a/PUMA axis on thyroid tumorigenesis were finally validated in murine models. We ultimately confirmed the anti-proliferative and pro-apoptotic effect of miR-30d via suppressing USP22 through in vivo findings. Conclusively, our findings highlight that the occurrence and progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22 via the SIRT1/FOXO3a/PUMA axis, which provides a attractive therapeutic target for thyroid cancer treatment.

USP22 promotes pro­inflammatory responses in Pseudomonas aeruginosa­induced keratitis by targeting TRAF6.

Pseudomonas aeruginosa (PA)­induced keratitis is characterized by inflammatory epithelial edema, stromal infiltration, corneal ulceration and can lead to vision loss. The present study aimed to study the effect of ubiquitin­specific protease 22 (USP22) on PA­induced keratitis. Using RT­qPCR and western blotting, significantly increased expression of USP22 was identified in mouse corneas and cultured RAW264.7 cells following PA stimulation. In addition, the results of in vivo experiments, western blot assay and ELISA suggested that the silencing of USP22 attenuated disease progression, downregulated the NF­κB pathway and suppressed the expression of pro­inflammatory cytokines following PA stimulation. Notably, it was identified that the expression of tumor necrosis factor receptor­associated factor 6 (TRAF6) was decreased by silencing of USP22 and USP22 was found to remove lysine 48­linked poly­ubiquitination chains from TRAF6 to stabilize TRAF6 expression and these effects were clearly aggravated following PA infection.

Long non­coding RNA CTBP1­AS2 upregulates USP22 to promote pancreatic carcinoma progression by sponging miR­141­3p.

Long non­coding RNAs (lncRNAs) feature prominently in pancreatic carcinoma progression. The present study aimed to clarify the biological functions, clinical significance and underlying mechanism of lncRNA CTBP1 antisense RNA 2 (CTBP1­AS2) in pancreatic carcinoma. Reverse transcription­quantitative PCR was performed to assess the expression levels of CTBP1­AS2, microRNA (miR)­141­3p and ubiquitin­specific protease 22 (USP22) mRNA in pancreatic carcinoma tissues and cell lines. Western blotting was used to examine USP22 protein expression in pancreatic carcinoma cell lines. Loss­of­function experiments were used to analyze the regulatory effects of CTBP1­AS2 on proliferation, apoptosis, migration and invasion of pancreatic carcinoma cells. Dual­luciferase reporter assay was used to examine the binding relationship between CTBP1­AS2 and miR­141­3p, as well as between miR­141­3p and USP22. It was demonstrated that CTBP1­AS2 expression was markedly increased in pancreatic carcinoma tissues and cell lines. High CTBP1­AS2 expression was associated with advanced clinical stage and lymph node metastasis of patients. Functional experiments confirmed that knocking down CTBP1­AS2 significantly inhibited pancreatic carcinoma cell proliferation, migration and invasion, and promoted cell apoptosis. In terms of mechanism, it was found that CTBP1­AS2 adsorbed miR­141­3p as a molecular sponge to upregulate the expression level of USP22. In conclusion, lncRNA CTBP1­AS2 may be involved in pancreatic carcinoma progression by regulating miR­141­3p and USP22 expressions; in addition, CTBP1­AS2 may be a diagnostic biomarker and treatment target for pancreatic carcinoma.

miR-140 inhibits osteosarcoma progression by impairing USP22-mediated LSD1 stabilization and promoting p21 expression.

Osteosarcoma is a bone tumor frequently diagnosed in children and young adults. Despite advances in chemotherapy and surgical resection, tumors metastasize in 30% of osteosarcoma patients. In addition, side effects caused by chemotherapeutic drugs, as well as the development of chemoresistance, highlight the need to identify the molecular mechanisms involved in the pathogenesis of osteosarcoma. We compared 65 osteosarcoma samples to their adjacent normal tissues, as well as commercially obtained osteosarcoma cell lines with normal osteoblast cell lines, and identified a role for the microRNA (miR)-140/ubiquitin-specific protease 22 (USP22)/lysine-specific demethylase 1 (LSD1)/p21 axis in the development of osteosarcoma. Osteosarcoma tissues and cells exhibited poor miR-140 and p21 expression, whereas the expression of USP22 and LSD1 was increased. Overexpression of miR-140 inhibited cell proliferation, migration, and invasion and promoted cell apoptosis by directly targeting USP22, resulting in its decreased expression. Overexpression of USP22 reversed the effects of miR-140 overexpression in osteosarcoma cells. Overexpression of miR-140 or USP22 knockdown led to the ubiquitination and degradation of LSD1. miR-140 overexpression also suppressed tumorigenesis in vivo. This study revealed a role for miR-140 in the restriction of osteosarcoma development and identified miR-140 as a potential target for therapeutic intervention.

RETRACTED: Knockdown EZH2 attenuates cerebral ischemia-reperfusion injury via regulating microRNA-30d-3p methylation and USP22.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief as there are concerns about the reliability of the results. Concerns have been raised about a portion of Figure 5B, 'DMSO' group appears to contain image similarities with Figure 4e, 'Inhibitor NC' group, published in Yang et al., 2021 doi: 10.1080/15384101.2020.1856498. A portion of Figure 5B, 'DZNeP+miR-30d-3p antagomir' group appears to contain image similarities with Figure 4e, 'Inhibitor NC' group, published in Yang et al., 2021. Figure 7/G western blot bands have the same eyebrow shaped phenotype as many other publications as detailed here (https://pubpeer.com/publications/B26AE47AC0E71E0EF339B40893B2C2).

microRNA-362-3p targets USP22 to retard retinoblastoma growth via reducing deubiquitination of LSD1.

Accumulating evidence has reported the role of microRNA (miR) in retinoblastoma (RB). Therefore, the objective was to discuss how miR-362-3p exerted its function in RB cell progression via regulating ubiquitin-specific protease 2 (USP22) and lysine-specific histone demethylase 1 (LSD1). MiR-362-3p, USP22 and LSD1 expression in RB cells and tissues were tested. The biological functions of RB cells were detected via over-expressing miR-362-3p and down-regulating USP22. The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified. Down-regulated miR-362-3p and up-regulated USP22 and LSD1 were demonstrated in RB tissues and cells. Restoring miR-362-3p and depleting USP22 attenuated invasion, proliferation and migration, and facilitated apoptosis of RB cells. USP22 was a target gene of miR-362-3p. USP22 deubiquitinated LSD1 in RB. It is revealed that miR-362-3p targets USP22 and then restrains invasion, proliferation and migration while promotes apoptosis of RB via reducing LSD1 modified by deubiquitination.

BMSCs-derived exosomal microRNA-let-7a plays a protective role in diabetic nephropathy via inhibition of USP22 expression.

OBJECTIVE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. The molecular pathogenesis of DN is still poorly understood. This study was designed to investigate the protective effect of bone marrow mesenchymal stem cell (BMSCs)-derived exosome (Exo)-transported microRNA-let-7a (miR-let-7a) on DN by targeting ubiquitin-specific protease 22 (USP22). METHODS: BMSCs of rats were cultured, and exosomes were identified. A rat models of DN were established in this study, and the rats were injected with Exo, Exo-let-7a mimic, or si-USP22 to figure their functions in renal function indicators blood urea nitrogen (BUN) and serum creatinine (SCr), blood lipid-related indicators total cholesterol (TC) and triglyceride (TG), renal cell apoptosis, oxidative stress, and expression of N-cadherin and vimentin in renal tissues. MiR-let-7a and USP22 targeting relationship was validated. RESULTS: Suppressed miR-let-7a and over-expressed USP22 exhibited in renal tissues of DN rats. Exosomes increased miR-let-7a and repressed USP22 in renal tissues of DN rats. Moreover, elevated exosomal miR-let-7a or silenced USP22 reduced SCr, BUN, TG and TC, suppressed apoptosis of renal cells and oxidative stress, and inhibited N-cadherin and vimentin expression in renal tissues of DN rats. MiR-let-7a had a targeting relationship with USP22. CONCLUSION: Our study highlights that BMSCs-derived exosomal miR-let-7a represses renal cell apoptosis, which plays a protective role in DN through down-regulation of USP22.

USP22 promotes proliferation in renal cell carcinoma by stabilizing survivin.

Renal cell carcinoma (RCC) is one of the commonest urological tumors. The incidence of RCC ranks third among urological tumors, after prostate cancer and bladder tumors. However, the etiology of RCC remains unclear. Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, is associated with the occurrence and progression of numerous tumors. However, the roles of USP22 in RCC have not yet been investigated. Survivin is a member of the inhibitor of apoptotic protein family involved in RCC progression. The present study first detected the expression of USP22 and survivin in RCC tissues using immunohistochemistry and western blotting. It was revealed that the protein levels of USP22 and survivin in RCC tissues were higher than those in adjacent normal renal tissue. Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved-caspase-3. By contrast, overexpression of USP22 promoted the growth of ACHN cells, upregulated the expression of survivin and decreased the level of cleaved-caspase-3. Notably, the changes in USP22 expression did not affect the SURVIVIN mRNA level. Finally, it was confirmed that USP22 interacted with survivin and stabilized it by downregulating its ubiquitination. The present results indicate that USP22 may regulate survivin via deubiquitination, thereby promoting the proliferation of RCC cells. The results of the current study suggest that USP22 may represent a novel therapeutic target for patients with RCC.

Ubiquitin-specific protease 22 is associated with poor prognosis in neuroblastoma.

BACKGROUND: Ubiquitin-specific protease 22 (USP22) alters histone ubiquitination and is considered to be an oncogenic factor involved in tumor progression. The USP22 aberrance has been implicated in several malignancies, but whether USP22 plays a role in neuroblastoma (NB) remains unclear. To the best of our knowledge, the clinicopathological significance of USP22 expression in NB has not been previously reported in the English-language medical literature. OBJECTIVES: The aim of this study was to investigate the role of USP22 and its association with potential targets in patients with NB. MATERIAL AND METHODS: The potential clinicopathological significance of USP22 expression in NB was studied using immunohistochemistry, immunohistochemical staining assessment and statistical analyses. RESULTS: Based on the immunohistochemical analysis, the USP22 protein was detected more manifestly in NB tissues than in healthy peritumoral tissue. Furthermore, an association between USP22, lymph node metastasis and NB clinical stage was observed, whereby the level of USP22 protein was higher in stage III-IV specimens than in stage I-II specimens (p < 0.05). Furthermore, tumors expressing USP22 were associated with poorer patient prognosis than the USP22-negative tumors. The multivariate Cox regression analysis suggested that the level of USP22 protein is a predictive factor for survival (p < 0.05). CONCLUSIONS: Our results indicate a significant association between USP22 level and poor prognosis in NB. Thus, USP22 represents a valuable biomarker for predicting the outcome of patients with NB.

Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury.

BACKGROUND: Intestinal ischemia reperfusion (I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22 (USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice. AIM: To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury. METHODS: An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion. Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo. siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22, Cyclin D1, and proliferating cell nuclear antigen (PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival (viability) and cell cycle were evaluated using the Cell Counting Kit-8 and flow cytometry, respectively. RESULTS: USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro, which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group (P < 0.05), while opposite results were observed in the USP22 overexpression group (P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration. CONCLUSION: USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury.

Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma.

Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin-specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora-B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora-B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora-B (P<0.01), Survivin (P<0.01), and Ki-67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin-dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora-B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future.

Targeting CD26 suppresses proliferation of malignant mesothelioma cell via downmodulation of ubiquitin-specific protease 22.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is associated with a poor prognosis, partly due to the lack of a precise understanding of the molecular mechanisms associated with its malignant behavior. In the present study, we expanded on our previous studies on cell cycle control of MPM cells by targeting CD26 molecule with humanized anti-CD26 monoclonal antibody (HuCD26mAb), focusing particularly on ubiquitin-specific protease 22 (USP22). We showed that USP22 protein expression is detected in clinical specimens of MPM and that USP22 knockdown, as well as CD26 knockdown, significantly inhibits the growth and proliferation of MPM cells in vitro and in vivo. Moreover, depletion of both USP22 and CD26 suppresses MPM cell proliferation even more profoundly. Furthermore, expression levels of USP22 correlate with those of CD26. HuCD26mAb treatment induces a decrease in USP22 level through its interaction with the CD26 molecule, leading to increased levels of ubiquitinated histone H2A and p21. By demonstrating a CD26-related linkage with USP22 in MPM cell inhibition induced by HuCD26mAb, our present study hence characterizes USP22 as a novel target molecule while concurrently suggesting a new therapeutic strategy for MPM.

Ubiquitin-specific protease 22 promotes the proliferation, migration and invasion of glioma cells.

Ubiquitin-specific protease 22 (USP22), as one of the 11 death-from-cancer signature genes, presented high expression in a variety of tumors. Previous studies showed that USP22 played a significant role in cell-cycle, oncogenesis, clinicopathology and survival. Our studies have presented USP22 was over-expressed in glioma tissue and the patients with high expression of USP22 had a poor survival than that with low expression of USP22. However, the concrete effect of USP22 on biological behavior in glioma cells has been rarely reported. The study aimed to clear the effect of USP22 on cell proliferation, migration and invasion in glioma. Using siRNA, USP22 was knocked down in U251 and U87 glioma cells and successful transfection effect was validated. Cell proliferation, migration and invasion were observed by the methods of EdU, Wound healing and Transwell assay, separately. At the same time, the expression of MMP2 was detected by Gelatin zymography after transfecting siRNAs. After the knockdown of USP22 by siRNA, the abilities of glioma cell proliferation, migration and invasion were decreased, accompanying, the expression of MMP2 was also decreased. We drew a conclusion that USP22 could increase the abilities of proliferation, migration and invasion of glioma cells, and promote the growth and development of glioma.

Prognostic and clinicopathological significance of ubiquitin-specific protease 22 overexpression in cancers: evidence from a meta-analysis.

PURPOSE: This meta-analysis study aimed to reveal the prognostic relevance of ubiquitin-specific protease 22 (USP22) expression in patients with cancers. METHODS: PubMed, Embase, and the Cochrane Library electronic databases were searched for relevant studies published up to April 2017. The prognostic value of USP22 expression was evaluated by hazard ratio with 95% confidence intervals (CIs). Relative risk (RR) with 95% CIs assessed the effects of USP22 expression on clinicopathological parameters. A total of 16 studies of 2,233 Chinese patients were included in the final meta-analysis. RESULTS: A significant association was found between USP22 overexpression and survival in patients with cancers. The pooled RR indicated that USP22 overexpression was related to histological grade, advanced tumor-node-metastasis stage, positive lymph node metastasis, and distant metastasis. CONCLUSION: This meta-analysis demonstrated that USP22 could be a novel biomarker for predicting prognosis in patients with cancers in the Chinese population.

MiR-101 targets USP22 to inhibit the tumorigenesis of papillary thyroid carcinoma.

Increasing evidence suggests that microRNA-101 (miR-101) is involved in the progression of various human cancers, including papillary thyroid carcinoma (PTC). However, the biological functions of miR-101 and underlying molecular mechanisms in PTC remain largely unknown. In this study, we demonstrated that miR-101 underexpression in PTC tissue was associated with lymph node metastasis and poor prognosis of PTC patients. MiR-101 reduced PTC cell proliferation, apoptosis resistance, and invasion. Ubiquitin-specific protease 22 (USP22) was confirmed as a direct target of miR-101. USP22 restoration attenuated the inhibitory effects of miR-101 on PTC malignant traits in vitro. In vivo, miR-101 overexpression or USP22 depletion reduced the tumorigenesis of PTC. Overall, our findings provide new insight into the mechanism of PTC inhibition by miR-101, suggesting the potential of miR-101 as a therapeutic target in PTC patients.