LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis.

Triple-negative breast cancer (TNBC) is the most lethal subtype of BC, with unfavorable treatment outcomes. Evidence suggests the engagement of lncRNA MCM3AP-AS1 in BC development. This study investigated the action of MCM3AP-AS1 in chemoresistance of TNBC cells. Drug-resistant TNBC cell lines SUM159PTR and MDA-MB-231R were constructed by exposure to increasing concentrations of doxorubicin/docetaxel (DOX/DXL). MCM3AP-AS1 and miR-524-5p expression levels were determined by RT-qPCR. RNA binding motif 39 (RBM39) level was measured using Western blot. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The targeted binding of miR-524-5p with MCM3AP-AS1 or RBM39 was predicted by ECORI database and validated by dual-luciferase assays. The gain-and-loss of function assays were conducted in cells to investigate the interactions among MCM3AP-AS1, miR-524-5p, and RBM39. TNBC xenograft mouse models were established through subcutaneous injection of MCM3AP-AS1-silencing MDA-MB-231R cells and intraperitoneally administrated with DOX/DXL to verify the role of MCM3AP-AS1 in vivo. MCM3AP-AS1 was upregulated in drug-resistant TNBC cells, and MCM3AP-AS1 silencing could sensitize drug-resistant TNBC cells to chemotherapeutic drugs by promoting apoptosis. MCM3AP-AS1 targeted miR-524-5p. After DOX/DXL treatment, miR-524-5p inhibition partially reversed the effect of MCM3AP-AS1 silencing on inhibiting chemoresistance and promoting apoptosis of drug-resistant TNBC cells. miR-524-5p targeted RBM39. Silencing MCM3AP-AS1 promoted apoptosis via the miR-524-5p/RBM39 axis, thereby enhancing chemosensitivity of drug-resistant TNBC cells. MCM3AP-AS1 knockdown upregulated miR-524-5p, downregulated RBM39, and restrained tumor development in vivo. MCM3AP-AS1 silencing potentiates apoptosis of drug-resistant TNBC cells by upregulating miR-524-5p and downregulating RBM39, thereby suppressing chemoresistance in TNBC.

Extracellular vesicles derived from cervical cancer cells carrying MCM3AP-AS1 promote angiogenesis and tumor growth in cervical cancer via the miR-93/p21 axis.

Tumor cells can promote angiogenesis by secreting extracellular vesicles (EVs). Meanwhile, tumor-derived EVs can carry long non-coding RNAs to activate pro-angiogenic signaling in endothelial cells. Here, we investigated the role of long non-coding RNA MCM3AP-AS1 carried by cervical cancer (CC) cell-derived EVs in the angiogenesis and the resultant tumor growth in CC, as well as the potential molecular mechanisms. LncRNAs significantly expressed in CC cell-derived EVs and CC were screened, followed by prediction of downstream target genes. EVs were isolated from HcerEpic and CaSki cell supernatants, followed by identification. The expression of MCM3AP-AS1 in CC was analyzed and its interaction with miR-93-p21 was confirmed. Following co-culture system, the role of MCM3AP-AS1 carried by EVs in HUVEC angiogenic ability, CC cell invasion and migration in vitro along with angiogenesis and tumorigenicity in vivo was assayed. MCM3AP-AS1 was overexpressed in CC cell-derived EVs as well as in CC tissues and cell lines. Cervical cancer cell-derived EVs could transfer MCM3AP-AS1 into HUVECs where MCM3AP-AS1 competitively bound to miR-93 and upregulate the expression of the miR-93 target p21 gene. Thus, MCM3AP-AS1 promoted angiogenesis of HUVECs. In the similar manner, MCM3AP-AS1 enhanced CC cell malignant properties. In nude mice, EVs-MCM3AP-AS1 induced angiogenesis and tumor growth. Overall, this study reveals that CC cell-derived EVs may transport MCM3AP-AS1 to promote angiogenesis and tumor growth in CC.

SOX4-activated lncRNA MCM3AP-AS1 aggravates osteoarthritis progression by modulating miR-149-5p/Notch1 signaling.

OBJECTIVE: To clarify the expression and underlying network of long non-coding RNA (lncRNA) MCM3AP-AS1 in osteoarthritis (OA). METHODS: Human articular cartilage samples, OA model rats and IL-1ß-treated C28/I2 cells were used in this study. The expression changes of genes and proteins were assessed by real-time quantitative PCR (qRT-PCR) and western blot. Cell viability, apoptosis, autophagy and extracellular matrix (ECM) degradation were assessed by Cell Counting Kit-8 (CCK-8), immunohistochemistry (IHC), flow cytometry, immunofluorescence and western blot assays, respectively. Molecule interactions were validated by dual luciferase and Chromatin immunoprecipitation (ChIP) assays. H&E staining was used to detect the pathological changes of cartilage. RESULTS: MCM3AP-AS1 was upregulated in OA patients and IL-1ß-induced chondrocytes. Knockdown of MCM3AP-AS1 enhanced autophagy, while alleviated ECM degradation and cartilage injury. Mechanistically, overexpression of SOX4 boosted the transcription of MCM3AP-AS1. Moreover, MCM3AP-AS1 functioned as a molecular sponge or epigenetic regulator of miR-149-5p to facilitate Notch1 expression. Functional rescue experiments showed that either inhibition of miR-149-5p nor ectopic expression of Notch1 dramatically weakened the biological impacts of MCM3AP-AS1 silencing. CONCLUSION: These finding demonstrated that SOX4-activated MCM3AP-AS1 aggravated OA progression by modulating autophagy and ECM degradation via targeting miR-149-5p/Notch1 axis. These data supported that inhibition of MCM3AP-AS1 might be a potential treatment strategy of OA.

A review on the role of MCM3AP-AS1 in the carcinogenesis and tumor progression.

Minichromosome Maintenance Complex Component 3 Associated Protein Antisense 1 (MCM3AP-AS1) is an RNA gene located on 21q22.3. The sense transcript from this locus has dual roles in the pathogenesis of solid tumors and hematological malignancies. MCM3AP-AS1 has been shown to sequester miR-194-5p, miR-876-5p, miR-543-3p, miR-28-5p, miR-93, miR-545, miR-599, miR-193a-5p, miR-363-5p, miR-204-5p, miR-211-5p, miR-15a, miR-708-5p, miR-138, miR-138-5p, miR-34a, miR-211, miR-340-5p, miR-148a, miR-195-5p and miR-126. Some cancer-related signaling pathway, namely PTEN/AKT, PI3K/AKT and ERK1/2 are influenced by this lncRNA. Cell line studies, animal studies and clinical studies have consistently reported oncogenic role of MCM3AP-AS1 in different tissues except for cervical cancer in which this lncRNA has tumor suppressor role. In the current manuscript, we collected evidence from these three sources of evidence to review the impact of MCM3AP-AS1 in the carcinogenesis.

LncRNA MCM3AP-AS1 sponges miR-148a to enhance cell invasion and migration in small cell lung cancer.

BACKGROUND: MCM3AP-AS1 is a recently characterized lncRNA playing an oncogenic role in several cancers. However, its role in lung cancer remains unknown. Here, we aimed to explore the functions of MCM3AP-AS1 in small cell lung cancer (SCLC) and the possible underlying mechanisms. METHODS: MCM3AP-AS1 and ROCK1 levels in SCLC patients were analyzed by qPCR. RNA pull-down and luciferase assays were performed to analyze the interaction between MCM3AP-AS1 and miR-148a. ROCK1 mRNA and protein levels were detected by qPCR and Western blot, respectively. Cell invasion and migration were analyzed by Transwell assays. RESULTS: MCM3AP-AS1 was upregulated in patients with SCLC, and a high MCM3AP-AS1 level was accompanied by a low survival rate. The binding of MCM3AP-AS1 to miR-148a predicted by bioinformatics analysis was verified by RNA pull-down and luciferase assays. However, MCM3AP-AS1 and miR-148a did not affect each other's expression. ROCK1 was upregulated in SCLC tissues and positively correlated with MCM3AP-AS1. In SCLC cells, MCM3AP-AS1 overexpression increased ROCK1 and promoted cancer cell invasion and migration, while miR-148a overexpression showed the opposite effects and attenuated the effects of MCM3AP-AS1 overexpression on ROCK1 expression and cell behaviors. CONCLUSIONS: MCM3AP-AS1 sponges miR-148a, thereby increasing SCLC cell invasion and migration via upregulating ROCK1 expression.

The MCM3AP-AS1/miR-126/VEGF axis regulates cancer cell invasion and migration in endometrioid carcinoma.

BACKGROUND: Long non-coding RNA (lncRNA) MCM3AP-AS1 plays an oncogenic role in several malignancies, but its role in endometrioid carcinoma (EC) is unclear. This study was carried out to explore the role of MCM3AP-AS1 in EC. METHODS: A total of 60 EC patients were enrolled in this study. Expression levels of MCM3AP Antisense RNA 1 (MCM3AP-AS1), microRNA-126 (miR-126), and vascular endothelial growth factor (VEGF) in tissues and transfetced cells were measured by RT-qPCR. Cell transfections were performed to explore the interaction among MCM3AP-AS1, miR-126 and VEGF. Transwell assays were perfromed to evaluate the invasion and migration abilities of HEC-1 cells after transfection. RESULTS: MCM3AP-AS1 was upregulated in EC and predicted poor survival. MCM3AP-AS1 directly interacted with miR-126. In EC cells, overexpression of MCM3AP-AS1 and miR-126 did not significantly affect the expression of each other. In addition, overexpression of MCM3AP-AS1 increased the expression levels of VEGF, a target of miR-126. Moreover, overexpression of MCM3AP-AS1 and VEGF increased the migration and invasion rates of EC cells, while overexpression of miR-126 suppressed these cell behaviors. Overexpression of MCM3AP-AS1 attenuated the role of miR-126 in cell invasion and migration. CONCLUSIONS: Therefore, MCM3AP-AS1 may serve as a competing endogenous RNA (ceRNA) of miR-126 to upregulate VEGF, thereby regulating cancer cell behaviors in EC.

YY1-mediated overexpression of long noncoding RNA MCM3AP-AS1 accelerates angiogenesis and progression in lung cancer by targeting miR-340-5p/KPNA4 axis.

Lung cancer is famous as an aggressive malignant tumor and is the main cause of cancer-associated mortality globally. Tumor angiogenesis is a vital part in cancer, which influences cell proliferation and metastasis. Increasing studies have claimed that long noncoding RNAs (lncRNAs) were involved in the progression of several cancers. Based on previous studies, this study focused on the role and mechanism of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in lung cancer. At first, MCM3AP-AS1 expression was found to be elevated in lung cancer cells. Depletion of MCM3AP-AS1 repressed cell proliferation, migration, and angiogenesis in lung cancer cells. YY1 was confirmed to mediate MCM3AP-AS1 transcription in lung cancer cells. Moreover, the molecular mechanism investigation revealed that MCM3AP-AS1 could sponge miR-340-5p and elevate KPNA4 expression. On the basis of rescue assays, we identified that the overexpression of KPNA4 partly counteracted the suppressed effect of MCM3AP-AS1 knockdown on angiogenesis and progression in lung cancer cells. Conclusively, the YY1-mediated overexpression of MCM3AP-AS1 accelerated angiogenesis and progression in lung cancer by targeting miR-340-5p/KPNA4 axis, which highlighted the possibility of MCM3AP-AS1 as a promising therapeutic target for lung cancer.

MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells.

BACKGROUND: Although the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer. METHODS: Paired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A. RESULTS: MCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p. CONCLUSION: MCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the "ceRNA" to regulate the expression of WNT5A by targeting miR-876-5p.

Long non-coding RNA MCM3AP-AS1 promotes growth and migration through modulating FOXK1 by sponging miR-138-5p in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a type of malignant gastrointestinal tumor. Long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) has been reported to stimulate proliferation, migration and invasion in several types of tumors. However, the role of MCM3AP-AS1 in PC remains unclear. METHODS: MCM3AP-AS1, microRNA miR-138-5p (miR-138-5p) and FOXK1 levels were detected using quantitative real time PCR. Cell proliferation, migration and invasion were analyzed. Dual luciferase reporter assay was used to confirm the relationship between MCM3AP-AS1 and miR-138-5p, between miR-138-5p and FOXK1. Protein levels were identified using western blot analysis. RESULTS: MCM3AP-AS1 overexpression promoted proliferation, migration and invasion in PC cells. MCM3AP-AS1 silencing showed a suppressive effect on cell growth in PC cells. Moreover, MCM3AP-AS1 knockdown suppressed tumor growth in mice. Dual luciferase reporter assay demonstrated MCM3AP-AS1 could sponge microRNA-138-5p (miR-138-5p), and FOXK1 could bind with miR-138-5p. Positive correlation between MCM3AP-AS1 and FOXK1 was testified, as well as negative correlation between miR-138-5p and FOXK1. MCM3AP-AS1 promoted FOXK1 expression by targeting miR-138-5p, and MCM3AP-AS1 facilitated growth and invasion in PC cells by FOXK1. CONCLUSION: MCM3AP-AS1 promoted growth and migration through modulating miR-138-5p/FOXK1 axis in PC, providing insights into MCM3AP-AS1/miR-138-5p/FOXK1 axis as novel candidates for PC therapy from bench to clinic.

LncRNA MCM3AP-AS1 regulates miR-142-3p/HMGB1 to promote LPS-induced chondrocyte apoptosis.

BACKGROUND: The role of long non-coding RNA (lncRNA) Minichromosome Maintenance Complex Component 3 Associated Protein (MCM3AP) Antisense RNA 1 (MCM3AP-AS1) has been analyzed in liver cancer. But its role in osteoarthritis (OA) is unknown. Through bioinformatics analysis, we predicted that MCM3AP-AS1 may interact with miR-142-3p, which is a major player in OA. This study aimed to investigate the roles of MCM3AP-AS1 in OA and to explore its interactions with microRNA miR-142-3p. METHODS: Differential expressions of MCM3AP-AS1 in OA patients and healthy participants were analyzed by performing quantitative PCR (qPCR). To analyze the relationship between MCM3AP-AS1 and miR-142-3p, human chondrocytes were transfected with MCM3AP-AS1 over-expression vector and miR-142-3p mimic. MCM3AP-AS1, miR-142-3p and high mobility group protein B1 (HMGB1) mRNA expression levels were measured by qPCR. RESULTS: We found that MCM3AP-AS1 was up-regulated in OA. Bioinformatics analysis showed that MCM3AP-AS1 may interact with miR-142-3p, which can inhibit the apoptosis of chondrocytes. In addition, over-expression of MCM3AP-AS1 and miR-142-3p failed to affect the expression of each other. Instead, MCM3AP-AS1 over-expression led to up-regulated expressions of HMGB1, which is a target of miR-142-3p. Lipopolysaccharide (LPS) treatment led to the up-regulated expressions of MCM3AP-AS1 in chondrocytes. In cell apoptosis assay, MCM3AP-AS1 and HMGB1 over-expression led to increased apoptotic rate of chondrocytes. MiR-142-3p over-expression played an opposite role and attenuated the effects of MCM3AP-AS1 over-expression. CONCLUSIONS: MCM3AP-AS1 may regulate miR-142-3p/HMGB1 to promote LPS-induced chondrocyte apoptosis.

Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction.

The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.

Featured lncRNA-based signature for discriminating prognosis and progression of hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been implicated in carcinogenesis and progression of hepatocellular carcinoma (HCC). This study aimed to identify a robust lncRNA signature for predicting the survival of HCC patients. We performed an integrated analysis of the lncRNA expression profiling in The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma database to identify the prognosis-related lncRNA for the HCC. The HCC cohort was randomly divided into a training set (n = 250) and a testing set (n = 113). Following a two-step screening, we identified an 18-lncRNA signature risk score. The high-risk subgroups had significantly shorter survival time than the low-risk group in both the training set (P < 0.0001) and the testing set (P = 0.005). Stratification analysis revealed that the prognostic value of the lncRNA-based signature was independent of the tumor stage and pathologic stage. The area under the receiver operating characteristic curve (AUROC) of the 18-lncRNA signature risk score was 0.826 (95%CI, 0.764-0.888), 0.817 (95%CI, 0.759-0.876), and 0.799 (95%CI, 0.731-0.867) for 1-year, 3-year, and 5-year follow-up, respectively. Bioinformatics analyses indicated that the 18 lncRNA might mediate cell cycle, DNA replication processes, and canonical cancer-related pathways, in which MCM3AP-AS1 was a potential target for HCC. In conclusion, the 18-lncRNA signature was a robust predictive biomarker for the prognosis and progression of HCC.

Long noncoding RNA MCM3AP-AS1 attenuates sepsis-induced cardiomyopathy by improving inflammation, oxidative stress, and mitochondrial function through mediating the miR-501-3p/CADM1/STAT3 axis.

Oxidative stress and inflammation are highly important for sepsis-mediated myocardial damage. The long noncoding RNA (lncRNA) MCM3AP-AS1 is involved in inflammatory diseases, but its function in acute myocardial injury during sepsis has not been fully elucidated. LPS and cecal ligation and puncture (CLP) were used to construct in vitro and in vivo sepsis-induced myocardial damage models, respectively. qRT-PCR was used to evaluate alterations in MCM3AP-AS1 and miR-501-3p alterations. After the MCM3AP-AS1 and miR-501-3p knockdown or overexpression models were established, the viability, apoptosis, inflammation, oxidative stress, and mitochondrial function of the myocardial cells were examined. Dual luciferase activity assay, RNA immunoprecipitation, and fluorescence in situ hybridization (FISH) confirmed the correlation among MCM3AP-AS1, miR-501-3p, and CADM1. Previous studies revealed that MCM3AP-AS1 was downregulated in sepsis patients, myocardial cells treated with LPS, and in the CLP mouse sepsis model, whereas miR-501-3p expression was increased. MCM3AP-AS1 overexpression hampered myocardial damage mediated by LPS and abated inflammation, oxidative stress, and mitochondrial dysfunction in myocardial cells and THP-1 cells. In contrast, MCM3AP-AS1 knockdown or miR-501-3p overexpression promoted all the effects of LPS. In vivo, MCM3AP-AS1 overexpression increased the survival rate of CLP mice; ameliorated myocardial injury; decreased the levels of TNF-α, IL-1ß, IL-6, iNOS, COX2, ICAM1, VCAM1, PGE2, and MDA; and increased the levels of SOD, GSH-PX, Nrf2, and HO-1. Mechanistic studies demonstrated that MCM3AP-AS1 acted as a competitive endogenous RNA to repress miR-501-3p, enhance CADM1 expression, and dampen STAT3/nuclear factor-kappaB (NF-κB) activation. MCM3AP-AS1 suppresses myocardial injury elicited by sepsis by mediating the miR-501-3p/CADM1/STAT3/NF-κB axis.

LncRNA MCM3AP-AS1 serves as a competing endogenous RNA of miR-218 to upregulate GLUT1 in papillary thyroid carcinoma.

Objective: MCM3AP-AS1 has been characterized as an oncogenic long non-coding RNA (lncRNA) in several cancers including papillary thyroid cancer (PTC), but its role in PTC has not been fully elucidated. Considering the critical role of lncRNAs in cancer biology, further functional analysis of MCM3AP-AS1 in PTC may provide novel insights into PTC management. Subjects and methods: Paired tumor and non-tumor tissues were collected from 63 papillary thyroid carcinoma (PTC) patients. Expression levels of MCM3AP-AS1, miR-218 and GLUT1 in tissue samples were analyzed by qRT-PCR. Cell transfection was performed to explore the interactions among MCM3AP-AS1, miR-218 and GLUT1. Cell proliferation assay was performed to evaluate the effects of MCM3AP-AS1 and miR-218 on cell proliferation. Results: MCM3AP-AS1 accumulated to high levels in PTC tissues and was affected by clinical stage. MCM3AP-AS1 showed a positive correlation with GLUT1 across PTC tissues. RNA interaction prediction showed that MCM3AP-AS1 could bind to miR-218, which can directly target GLUT1. MCM3AP-AS1 and miR-218 showed no regulatory role regulating the expression of each other, but overexpression of MCM3AP-AS1 upregulated GLUT1 and enhanced cell proliferation. In contrast, overexpression of miR-218 downregulated GLUT1 and attenuated cell proliferation. In addition, miR-218 suppressed the role of MCM3AP-AS1 in regulating the expression of GLUT1 and cell proliferation. Conclusion: MCM3AP-AS1 may serve as a competing endogenous RNA of miR-218 to upregulate GLUT1 in PTC, thereby promoting cell proliferation. The MCM3APAS1/ miR-218/GLUT1 pathway characterized in the present study might serve as a potential target to treat PTC.

LncRNA MCM3AP-AS1 enhances cell invasion, migration and tumor formation in non-small cell lung cancer cells by epigenetic inhibition of miR-34a.

BACKGROUND: The function of long non-coding RNA (lncRNA) MCM3AP-AS1 has been reported in several types of cancer, while its involvement in non-small cell lung cancer (NSCLC) is unknown. OBJECTIVE: This study aimed to investigate the function of MCM3AP-AS1 in NSCLC. METHODS: Silencing or overexpression of MCM3AP-AS1 was achieved in tumor cells to construct a tumor-bearing mice model to evaluate the effects of MCM3AP-AS1 on tumor growth. RESULTS: The results showed that MCM3AP-AS1 was upregulated in NSCLC and associated with worse survival. In NSCLC tissues, MCM3AP-AS1 was inversely correlated with microRNA (miR)-34a. MCM3AP-AS1 led to enhanced NSCLC cell movement and proliferation. Overexpression of miR-34a rescued the effect of overexpression of MCM3AP-AS1 on cell movement. Xenograft experiments showed tumor weight and volume in the si­MCM3AP-AS1 group and the miR-34a group to be significantly reduced. MCM3AP-AS1 increased tumor weight and volume, and miR-34a partially attenuated MCM3AP-AS1-induced promotion of tumor growth. CONCLUSION: MCM3AP-AS1 may enhance cell invasion, migration, and tumor formation capacity by regulating miR-34a in NSCLC cells.

The role of LncRNA MCM3AP-AS1 in human cancer.

Long noncoding RNAs (lncRNA) play pivotal roles in every level of gene and genome regulation. MCM3AP-AS1 is a lncRNA that has an oncogenic role in several kinds of cancers. Aberrant expression of MCM3AP-AS1 has been reported to be involved in the progression of diverse malignancies, including colorectal, cervical, prostate, lymphoma, lung, ovary, liver, bone, and breast cancers. It is generally believed that MCM3AP-AS1 expression is associated with cancer cell growth, proliferation, angiogenesis, and metastasis. MCM3AP-AS1 by targeting various signaling pathways and microRNAs (miRNAs) presents an important role in cancer pathogenesis. MCM3AP-AS1 as a competitive endogenous RNA has the ability to sponge miRNA, inhibit their expressions, and bind to different target mRNAs related to cancer development. Therefore, MCM3AP-AS1 by targeting several signaling pathways, including the FOX family, Wnt, EGF, and VEGF can be a potent target for cancer prediction and diagnosis. In this review, we will summarize the role of MCM3AP-AS1 in various human cancers.

Long Non-Coding RNA MCM3AP-AS1: A Crucial Role in Human Malignancies.

The incidence of cancer continues to grow and is one of the leading causes of death in the world. Long noncoding RNAs (LncRNAs) is a group of RNA transcripts greater than 200 nucleotides in length, and although it cannot encode proteins, it can regulate different biological functions by controlling gene expression, transcription factors, etc. LncRNA micro-chromosome maintenance protein 3-associated protein antisense RNA 1 (MCM3AP-AS1) is involved in RNA processing and cell cycle-related functions, and MCM3AP-AS1 is dysregulated in expression in various types of cancers. This biomarker is involved in many processes related to carcinogens, such as cell proliferation, apoptosis, cell cycle, and migration. In this review, we summarize the roles of MCM3AP-AS1 in different human cancers and its biological functions with a view to providing ideas for future research.

LncRNA MCM3AP-AS1 is downregulated in diabetic retinopathy and promotes cell apoptosis by regulating miR-211/SIRT1.

AIM: This study aimed to investigate the role of lncRNA MCM3AP-AS1 in diabetic retinopathy (DR). METHODS: Plasma MCM3AP-AS1 levels in DR patients (n = 80), T2DM patients (n = 80), and Controls (n = 80) were measured by qPCR and compared using ANOVA (one-way) and Tukey test. The expressions of lncRNA MCM3AP-AS1 and miR-211 in Human retinal pigment epithelial cells (hRPE) line ARPE-19 were detected by RT-qPCR. Western blot and annexin V-FITC staining were performed to investigate the role of MCM3AP-AS1/SIRT1 in ARPE-19 cell proliferation and apoptosis in vitro. RESULTS: We observed that MCM3AP-AS1 was downregulated in DR patients 25 comparing to T2D patients without significantly complications. Bioinformatics analysis showed that MCM3AP-AS1 might bind miR-211. However, no significant correlation between these two factors was observed in DR patients. Consistently, overexpression of MCM3AP-AS1 and miR-211 failed to affect the expression of each other in hRPE. Interestingly, MCM3AP-AS1 overexpression upregulated SIRT1, a target of miR-211. Moreover, MCM3AP-AS1 was downregulated in DR patients compared to type 2 diabetic mellitus patients without significant complications. In RPEs, high glucose treatment downregulated MCM3AP-AS1. Cell apoptosis analysis showed that MCM3AP-AS1 and SIRT1 overexpression decreased the apoptotic rate of RPEs, and miR-211 overexpression reduced the effect of MCM3AP-AS1 and SIRT1 overexpression. CONCLUSION: MCM3AP-AS1 is downregulated in DR and promotes cell apoptosis by regulating miR-211/SIRT1.

MCM3AP-AS1: A LncRNA Participating in the Tumorigenesis of Cancer Through Multiple Pathways.

BACKGROUND: More and more shreds of evidence show that the occurrence and development of tumors are closely related to the abnormal expression of LncRNA. A large number of experiments have found that overexpression or under-expression of MCM3AP-AS1 can affect the occurrence and development of cancer cells in varying degrees, such as proliferation, invasion, and translocation. Besides, MCM3AP-AS1 may become a promising target for many tumor biotherapies. This article reviews the pathophysiological functions and molecular mechanisms of MCM3AP-AS1 in various tumors. METHODS: This paper systematically summarizes the published literatures in PubMed. The molecular mechanism of MCM3AP-AS1 in a variety of tumors is reviewed. RESULTS: The abnormal expression of MCM3AP-AS1 in different tumors is closely related to tumor proliferation, invasion, and migration. MCM3AP-AS1 mediates or participates in related signaling pathways to regulate the expression of targeted miRNAs and proteins. MCM3AP-AS1 plays a vital role in tumor diagnosis and treatment. CONCLUSION: LncRNA MCM3AP-AS1 is a feasible tumor marker and a potential therapeutic target for many kinds of tumors.

Overexpression of long noncoding RNA MCM3AP-AS1 promotes osteogenic differentiation of dental pulp stem cells via miR-143-3p/IGFBP5 axis.

MCM3AP-AS1 regulates the cartilage repair in osteoarthritis, but how it regulates osteogenic differentiation of dental pulp stem cells (DPSCs) remains to be determined. DPSCs were isolated and induced for osteogenic differentiation. MCM3AP-AS1 expression was increased along with the osteogenic differentiation of DPSCs, whose expression was positive correlated with those of OCN, alkaline phosphatase (ALP) and RUNX2. On contrary, miR-143-3p expression was decreased along with the osteogenic differentiation and was negatively correlated with those of OCN, ALP and RUNX2. Dual-luciferase reporter gene assay showed that miR-143-3p can be negatively regulated by MCM3AP-AS1 and can regulate IGFBP5. MCM3AP-AS1 overexpression increased the expression levels of osteogenesis-specific genes, ALP activity and mineralized nodules during DPSC osteogenic differentiation, while IGFBP5 knockdown or miR-143-3p overexpression counteracted the effect of MCM3AP-AS1 overexpression in DPSCs. Therefore, this study demonstrated the role of MCM3AP-AS1/miR-143-3p/IGFBP5 axis in regulating DPSC osteogenic differentiation.