[Corrigendum] miR­1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer.

Following the publication of the above article, a concerned reader drew to the authors' attention that the data shown for the 'CAOV3/NC mimics' experiment in Fig. 2D on p. 443 appeared to be the same as that shown for the 'TUG1­sh+miR­1299 inhibitors' experiment in Fig. 4H on p. 444. The authors have examined their original data, and realize that the same data was inadvertently included in the two figures. Consequently, the corrected version of Fig. 2, featuring the correct data for the 'CAOV3/NC mimics' experiment in Fig. 2D, is shown opposite. The overall conclusions of this study were not affected by this error. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused. [Oncology Reports 44: 438-448, 2020; DOI: 10.3892/or.2020.7623].

Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity.

Despite the rapid utilization of immunotherapy, emerging challenges to the current immune checkpoint blockade need to be resolved. Here, we report that elevation of CD73 levels due to its aberrant turnover is correlated with poor prognosis in immune-cold triple-negative breast cancers (TNBCs). We have identified TRIM21 as an E3 ligase that governs CD73 destruction. Disruption of TRIM21 stabilizes CD73 that in turn enhances CD73-catalyzed production of adenosine, resulting in the suppression of CD8+ T cell function. Replacement of lysine 133, 208, 262, and 321 residues by arginine on CD73 attenuated CD73 ubiquitylation and degradation. Diminishing of CD73 ubiquitylation remarkably promotes tumor growth and impedes antitumor immunity. In addition, a TRIM21high/CD73low signature in a subgroup of human breast malignancies was associated with a favorable immune profile. Collectively, our findings uncover a mechanism that governs CD73 proteolysis and point to a new therapeutic strategy by modulating CD73 ubiquitylation.

Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis.

Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed tryptophan metabolism during heart regeneration is largely unexplored. Here, we find that apical neonatal mouse heart resection surgery led to rapid and consistent increases in cardiac IDO1 expression and kynurenine accumulation. Cardiac deletion of Ido1 gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably, Ahr deletion prevents indoleamine 2,3 dioxygenase -kynurenine-associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.

Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE-/- mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS.

Pyroptosis correlates with tumor immunity and prognosis.

Pyroptosis, as a proinflammatory form of regulated cell death, plays an important role in multiple cancers. However, the diagnostic and prognostic values of pyroptosis and its interaction with tumor immunity in pan-cancer are still unclear. Here, we show an elevated general expression of 17 pyroptosis-associated genes of tumor patients with high-immune-activity and a reduced pyroptosis in low-immune-activity tumors. Moreover, pyroptosis is positively correlated with immune infiltration and immune-related signatures across 30 types of cancer. Furthermore, our experimental data suggest that pyroptosis directly modulate the expression of immune checkpoint molecules and cytokines. We generate a pyroptosis score model as a potential independent prognostic indicator in melanoma patients. Interestingly, 3 of pyroptosis-associated genes including CASP1, CASP4 and PYCARD, can predict the effectiveness of anti-PD-1 immunotherapy for patients with melanoma. Our study demonstrates that pyroptosis correlates with tumor immunity and prognosis, might be used as a potential target for immune therapy.

Ferroptosis Associates With Diagnosis and Prognosis by Promoting Antitumor Immune Response in Melanoma.

Immunotherapy has greatly improved the clinical benefits of cancer treatment, especially in melanoma. Ferroptosis is a novel mechanism of cell death which relates to immunity. This study aimed at understanding the potential link between ferroptosis and cancer immunocompetent in melanoma using multiple bioinformatics analyses. By the WGCNA assay, we first constructed a key module-gene of ferroptosis, which was strongly correlated with the diagnosis, prognosis, and infiltration of immune cells in melanoma. The elevated module-gene could effectively distinguish melanoma from normal tissues and acted as a good prognostic marker. The module-gene of ferroptosis was positively correlated with the infiltration of immune cells. In particular, the module was positively correlated with the expression of PD-L1 and sensitively increased after effective anti-PD-1 treatment. Furthermore, the differential expression of the module-gene between normal and tumor tissues was observed in pan-cancer. The similarity correlations of the module-gene with infiltration of immune cells and the expressions of PD-L1 were confirmed in the pan-cancer level. Our study demonstrated that the key module-gene of ferroptosis was closely related with diagnosis, prognosis, and anti-immune response in melanoma, as well as in pan-cancer.

Reducing N6AMT1-mediated 6mA DNA modification promotes breast tumor progression via transcriptional repressing cell cycle inhibitors.

DNA N6-methyladenosine (6mA) is a novel epigenetic signaling modification in humans and has been implicated in the progression and tumorigenesis of several cancers. However, the function and mechanism of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Here, we found that decreases in N6AMT1 correlated with the extent of 6mA in clinical BC tissues and predicted a worse survival of BC patients. Functionally, knockdown of N6AMT1 markedly reduced 6mA in DNA and promoted colony formation and migration of BC cells, whereas overexpression of N6AMT1 had the opposite effect. Moreover, silencing of N6AMT1 reduced 6mA modification and enhanced the growth of BC cells in vitro and tumors in vivo. 6mA immunoprecipitation sequencing (6mA-IP-seq), RNA-seq, 6mA-IP-PCR, and bioinformatics analysis indicated that N6AMT1 was a functional methyltransferase for genomic 6mA DNA modifications and related to gene transcriptional activity. Critical negative regulators of the cell cycle, such as RB1, P21, REST, and TP53 were identified as targets of N6AMT1 in BC. These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.

YTHDF1 Promotes Cyclin B1 Translation through m6A Modulation and Contributes to the Poor Prognosis of Lung Adenocarcinoma with KRAS/TP53 Co-Mutation.

KRAS and TP53 mutations are the two most common driver mutations in patients with lung adenocarcinoma (LUAD), and they appear to reduce latency and increase metastatic proclivity when a KRAS and TP53 co-mutation (KRAS/TP53-mut) occurs. However, the molecular mechanism involved is unclear. N6-methyladenosine (m6A), the most abundant RNA modification in mammal mRNAs, plays a critical role in tumorigenesis. Here, we used genomic and transcriptomic data and found that only LUAD patients with KRAS/TP53-mut, but not an individual mutation, appeared to exhibit poor overall survival when compared with patients without KRAS and TP53 mutation (wildtype). Subsequently, we analyzed the differential expression of the 15-m6A-related genes in LUAD with different mutations and found that YTHDF1 was the most upregulated in KRAS/TP53-mut patients and associated with their adverse prognosis. Bioinformatics and experimental evidence indicated that elevated YTHDF1 functionally promoted the translation of cyclin B1 mRNA in an m6A-dependent manner, thereby facilitating the tumor proliferation and poor prognosis of LUAD with KRAS/TP53-mut. Furthermore, the concurrent increase in YTHDF1 and cyclin B1 was confirmed by immunohistochemistry staining in patients with co-occurring KRAS/TP53 mutations. YTHDF1 was correlated with an unfavorable clinical stage and tumor size. Collectively, we identified and confirmed a novel "YTHDF1-m6A-cyclin B1 translation" axis as an essential molecular pathway for the prognosis of KRAS/TP53-mut LUAD.

HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster.

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster.

Suppression of m6A mRNA modification by DNA hypermethylated ALKBH5 aggravates the oncological behavior of KRAS mutation/LKB1 loss lung cancer.

Oncogenic KRAS mutations combined with the loss of the LKB1 tumor-suppressor gene (KL) are strongly associated with aggressive forms of lung cancer. N6-methyladenosine (m6A) in mRNA is a crucial epigenetic modification that controls cancer self-renewal and progression. However, the regulation and role of m6A modification in this cancer are unclear. We found that decreased m6A levels correlated with the disease progression and poor survival for KL patients. The correlation was mediated by a special increase in ALKBH5 (AlkB family member 5) levels, an m6A demethylase. ALKBH5 gain- or loss-of function could effectively reverse LKB1 regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells. Mechanistically, LKB1 loss upregulated ALKBH5 expression by DNA hypermethylation of the CTCF-binding motif on the ALKBH5 promoter, which inhibited CTCF binding but enhanced histone modifications, including H3K4me3, H3K9ac, and H3K27ac. This effect could successfully be rescued by LKB1 expression. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, SMAD7, and MYC, through a pathway dependent on YTHDF2, an m6A reader protein. The above findings were confirmed in clinical KRAS-mutated lung cancer patients. We conclude that loss of LKB1 promotes ALKBH5 transcription by a DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer.

Development of a Novel Multiple Cross-Linking Spiral Amplification for Rapid and Sensitive Detection of HPV16 DNA.

PCRThere has been increasing interest in the head and neck squamous cell carcinoma (HNSCC) that is caused by high-risk human papillomavirus (HR-HPV) and has posed a significant challenge to Otolaryngologists. A rapid, sensitive, and reliable method is required for the detection of HR-HPV in clinical specimens to prevent and treat HPV-induced diseases. In this study, a multiple cross-linking spiral amplification (MCLSA) assay was developed for the visual detection of HPV-16. In the MCLSA assay, samples were incubated under optimized conditions at 62°C for 45 min, and after mixing with the SYBR Green I (SGI) dye, the positive amplicons showed bright green fluorescence while the negative amplicons exhibited no obvious change. The specificity test revealed that the developed MCLSA technique had high specificity and could effectively distinguish all five HPV-16 strains from other pathogenic microorganisms. In terms of analytical sensitivity, the limit of detection (LoD) of MCLSA assay was approximately 5.4 × 101 copies/tube, which was 10-fold more sensitive than loop-mediated isothermal amplification (LAMP) and RT-PCR. The detection results of laryngeal cancer specimens collected from 46 patients with suspected HPV infection in the Liaoning region demonstrated that the positive detection rates of MCLSA and hybridized capture 2 kit were 32.61% (15/46). The true positive rate of the MCLSA assay was higher than that of RT-PCR (100% vs. 93.33%) and LAMP (100% vs. 86.67%). Therefore, the MCLSA assay developed in the present study could be a potentially useful tool for the point-of-care (PoC) diagnosis of HR-HPV, especially in resource-limited countries.

Peripheral Blood Leukocyte N6-methyladenosine is a Noninvasive Biomarker for Non-small-cell Lung Carcinoma.

BACKGROUND: N6-methyladenosine (m6A) triggers a new layer of epi-transcription. However, the potential noninvasive screening and diagnostic value of peripheral blood m6A for cancer are still unknown. Here, we intend to investigate whether leukocyte m6A can be a novel biomarker for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Peripheral blood was collected from 119 NSCLC patients and 74 age-matched healthy controls. Total RNA was isolated from leukocytes for m6A measurement, and clinical information of participants was reviewed. The sensitivity, specificity, and area under the curve (AUC) of m6A for cancer diagnosis were evaluated by the receiver-operating characteristic (ROC) curve analysis. Flow cytometry and the Human Protein Atlas (HPA) database were used to characterize m6A in leukocyte differentials. Pearson's correlation was applied to indicate the relationship between m6A level and hematology variables. qPCR and bioinformatic analysis were used to identity the expression of m6A regulators in leukocyte. RESULTS: Leukocyte m6A was significantly elevated in 119 NSCLC patients compared with 74 healthy controls (P<0.001). We did not find significant association between m6A and age or gender. Elevated m6A level in NSCLC was associated with tumor stage (P<0.05) and tumor differentiation (P<0.05), and was significantly reduced after surgery (P<0.01). ROC curve analysis revealed that leukocyte m6A could significantly discriminate patients with lung adenocarcinoma (LUAD) (AUC=0.736, P<0.001) and lung squamous cell carcinoma (LUSC) (AUC=0.963, P<0.001) from healthy individuals. m6A displayed superior sensitivity (100%) and specificity (85.7%) for LUSC than squamous cell carcinoma (SCC) antigen and cytokeratin fragment 211 (Cyfra211). Flow cytometry analysis showed m6A modification was mainly localized on T cells and monocytes among leukocyte differentials. Leukocyte m6A was positively correlated with the number of lymphocytes and negatively correlated with monocytes in NSCLC but not in healthy controls. qPCR and bioinformatic analysis showed that elevated leukocyte m6A in NSCLC was caused by upregulated methyltransferase complex and downregulated FTO and ALKBH5. CONCLUSION: Leukocyte m6A represents a potential noninvasive biomarker for NSCLC screening, monitoring and diagnosis.

MicroRNA­491­5p inhibits trophoblast cell migration and invasion through targeting matrix metalloproteinase­9 in preeclampsia.

Insufficient invasion of trophoblasts is correlated with the development of preeclampsia (PE). MicroRNA (miR)­491­5p has been reported to be implicated in human cancer cell invasion; however, whether miR­491­5p is involved in the development of PE remains largely unclear. The aim of the present study was to investigate the role of miR­491­5p in trophoblastic invasion in vitro and to determine its underlying mechanism of action. The expression levels of miR­491­5p were validated using reverse transcription­quantitative PCR. The effects of miR­491­5p on trophoblast cell invasion were evaluated in vitro. Then, the association between miR­491­5p and its downstream target was investigated in both cell lines and clinical specimens. miR­491­5p expression levels were observed to be significantly increased in the placental tissues from patients with PE. The invasive capacity of HTR­8/SVneo trophoblast cells was suppressed following the upregulation of miR­491­5p and increased following the inhibition of miR­491­5p. Matrix metalloproteinase­9 (MMP­9), a well­known regulator of trophoblast cell invasion, was discovered to be a direct target of miR­491­5p in HTR­8/SVneo trophoblast cells. Moreover, miR­491­5p expression levels were found to be inversely correlated with MMP­9 expression levels in placental tissues from patients with PE. The overexpression of MMP­9 partly attenuated the inhibitory effects of miR­491­5p on HTR­8/SVneo trophoblast cells invasion. Collectively, these findings suggested that the aberrant expression of miR­491­5p may contribute to PE through suppressing trophoblast invasion, thus highlighting the novel roles of miR­491­5p in the molecular pathogenesis of PE. The present study also showed that the miR­491­5p/MMP­9 axis may be an effective biomarker or a viable drug target for therapeutic intervention in PE.

Long-Chain Non-Coding RNA SNHG3 Promotes the Growth of Ovarian Cancer Cells by Targeting miR-339-5p/TRPC3 Axis.

BACKGROUND: Long-chain non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is reportedly overexpressed in malignant tumors, but its regulatory role in human ovarian cancer (OC) is not fully understood. METHODS: A qRT-PCR assay was carried out to detect the level of SNHG3 in OC tissues, serum and cells, a CCK-8 assay to measure the proliferation of OC cells, a transwell assay to measure the invasion and migration of OC cells, and a flow cytometry to detect the cell cycle distribution and apoptosis rate of OC cells. In addition, in vivo experiment was also conducted to determine the effect of SNHG3 on the growth of OC cells. RESULTS: SNHG3 was overexpressed in OC tissues, serum, and cells, and the overexpression in serum indicated a poor prognosis of patients. It was also found that knockdown of SNHG3 could inhibit the malignant phenotypes of OC cells, cause G1/G0 cell cycle arrest, and intensify apoptosis. Furthermore, in in vitro experiments, the growth ability of OC cells was inhibited under knockdown of SNHG3. Assays for relationship verification showed that SNHG3 regulated the expression of miR-339-5p and the canonical transient receptor potential 3 (TRPC3), and the rescue experiment revealed that co-transfection of si-SNHG3+miR-339-5p-inhibitor or si-SNHG3+pcDNA3.1-TRPC3 could reverse the effects of knockdown of SNHG3 on the biological behavior of OC cells. CONCLUSION: SNHG3 can be adopted as a marker for diagnosis and prognosis evaluation of OC and it plays a role in the progression of OC by enabling the miR-339-5p sponge to regulate TRPC3 expression.

Long Noncoding RNA KCNMB2-AS1 Stabilized by N6-Methyladenosine Modification Promotes Cervical Cancer Growth Through Acting as a Competing Endogenous RNA.

Long noncoding RNA (lncRNA) is emerging as an essential regulator in the development and progression of cancer, including cervical cancer (CC). In this study, we found a CC-related lncRNA, KCNMB2-AS1, which was significantly overexpressed in CC and linked to poor outcomes. Depletion of KCNMB2-AS1 remarkably inhibited CC cell proliferation and induced apoptosis. In vivo xenograft models revealed that knockdown of KCNMB2-AS1 evidently delayed tumor growth. Mechanistically, KCNMB2-AS1 was predominantly located in the cytoplasm and served as a competing endogenous RNA to abundantly sponge miR-130b-5p and miR-4294, resulting in the upregulation of IGF2BP3, a well-documented oncogene in CC. Moreover, IGF2BP3 was able to bind KCNMB2-AS1 by three N6-methyladenosine (m6A) modification sites on KCNMB2-AS1, in which IGF2BP3 acted as an m6A "reader" and stabilized KCNMB2-AS1. Thus, KCNMB2-AS1 and IGF2BP3 formed a positive regulatory circuit that enlarged the tumorigenic effect of KCNMB2-AS1 in CC. Together, our data clearly suggest that KCNMB2-AS1 is a novel oncogenic m6A-modified lncRNA in CC, targeting KCNMB2-AS1 and its related molecules implicate the therapeutic possibility for CC patients.

miR­1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer.

Recent studies have revealed the oncogenic role of notch reporter 3 (NOTCH3) in ovarian cancer (OC). However, the possible regulators and mechanisms underlying notch receptor 3 (NOTCH3)­mediated behaviors in OC remain to be completely investigated. In the present study, we aimed to identify regulators of NOTCH3 and their interactions underlying the pathogenesis of OC. Bioinformatics analysis and luciferase reporter assay were used to identify potential regulatory miRNAs and lncRNAs of NOTCH3 in OC. Several in vivo and in vitro assays were performed to evaluate their effects on the proliferative ability mediated by NOTCH3. We identified microRNA­1299 (miR­1299) as a novel negative regulator of NOTCH3. miR­1299 was downregulated in OC and was found to be considerably correlated with tumor differentiation. Upregulation of miR­1299 inhibited cell proliferation, colony formation, and 5­ethynyl­2'­deoxyuridine (EdU) incorporation, as well as induced cell cycle arrest in the G0G1 phase in OC cells. Overexpression of miR­1299 in xenograft mouse models suppressed tumor growth in vivo. The lncRNA taurine upregulated gene 1 (TUG1), acting as a sponge of miR­1299, was found to upregulate NOTCH3 expression and promote cell proliferation in OC through the competing endogenous RNA mechanism. In addition, TUG1 was found to be a potential downstream target of NOTCH3, forming a miR­1299/NOTCH3/TUG1 feedback loop in the development of OC. Collectively, our findings improve the understanding of NOTCH3­mediated regulation in OC pathogenesis and facilitate the development of miRNA­ and lncRNA­directed diagnostics and therapeutics against this disease.

CTRP13 Preserves Endothelial Function by Targeting GTP Cyclohydrolase 1 in Diabetes.

Endothelial dysfunction plays a crucial role in the progress of diabetic vasculopathy. C1q/tumor necrosis factor-related protein 13 (CTRP13) is a secreted adipokine that can ameliorate atherosclerosis and vascular calcification. However, the role of CTRP13 in regulating endothelial function in diabetes has yet to be explored. In this study, CTRP13 treatment improved endothelium-dependent relaxation in the aortae and mesenteric arteries of both db/db mice and streptozotocin-injected mice. CTRP13 supplement also rescued the impaired endothelium-dependent relaxation ex vivo in the db/db mouse aortae and in high glucose (HG)-treated mouse aortae. Additionally, CTRP13 treatment reduced reactive oxygen species overproduction and improved nitric oxide (NO) production and endothelial NO synthase (eNOS) coupling in the aortae of diabetic mice and in HG-treated human umbilical vein endothelial cells. Mechanistically, CTRP13 could increase GTP cyclohydrolase 1 (GCH1) expression and tetrahydrobiopterin (BH4) levels to ameliorate eNOS coupling. More importantly, CTRP13 rescued HG-induced inhibition of protein kinase A (PKA) activity. Increased PKA activity enhanced phosphorylation of the peroxisome proliferator-activated receptor α and its recruitment to the GCH1 promoter, thus activating GCH1 transcription and, ultimately, endothelial relaxation. Together, these results suggest that CTRP13 preserves endothelial function in diabetic mice by regulating GCH1/BH4 axis-dependent eNOS coupling, suggesting the therapeutic potential of CTRP13 against diabetic vasculopathy.

MiR-93 blocks cell cycle progression and promotes apoptosis in uterine leiomyoma cells by targeting CCND1.

Uterine leiomyoma (UL) is the most common type of benign tumor in the women's reproductive system. A number of genes has been found to play an important role in the initiation and progression of UL, including miRNAs. In this study, our results exhibited that miR-93, a member of mir-106b-25 cluster, significantly reduced the cell viability, promoted cell cycle arrest, caused apoptosis, and inhibited migration in UL cells (p < .01). Moreover, our results have provided experimental evidence that miR-93 regulated the biological functions of UL cells by targeting CCND1.