lncRNA MT1JP Research Articles

Retraction.

Retraction: "LncRNA MT1JP functions as a tumor suppressor via regulating miR-214-3p expression in bladder cancer" by Haifeng Yu, Shuaibin Wang, Haibo Zhu, and Dapang Rao, J Cell Physiol. 2019; 16160-16167: The above article, published online on 20 February 2019 in Wiley Online Library https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28274), has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. Thus, the conclusions are considered to be invalid.

LncRNA MT1JP-overexpression abolishes the silencing of PTEN by miR-32 in hepatocellular carcinoma.

Previous studies have shown that long non-coding RNA (lncRNA) MT1JP plays a role as a tumor suppressor in several types of cancer. The present study aimed to explore the role of MT1JP in hepatocellular carcinoma (HCC). Paired HCC and non-tumor tissues from 64 patients with HCC were subjected to RNA isolation and reverse transcription-quantitative PCR (RT-qPCR) to analyze the differential expression of MT1JP, microRNA (miR)-32 and phosphatase and tensin homolog (PTEN) in HCC. Cell transfections, followed by RT-qPCR and western blotting, were carried out to investigate the interactions among MT1JP, miR-32 and PTEN. The role of MT1JP, miR-32 and PTEN in regulating HCC cell proliferation was assessed using a Cell Counting Kit-8 assay. It was found that MT1JP was downregulated in HCC cancer tissues compared with that in non-cancer tissues. Survival analysis showed that patients with low MT1JP expression levels exhibited a significantly higher 5-year overall survival rate compared with patients with high MT1JP levels. The expression of MT1JP in HCC tissues was positively associated with PTEN and negatively associated with miR-32. Overexpression of MT1JP increased the expression levels of PTEN and decreased the expression levels of miR-32. Overexpression of miR-32 did not affect the expression of MT1JP but decreased the expression levels of PTEN and attenuated the effect of overexpression of MT1JP on the expression of PTEN. Overexpression of MT1JP and PTEN decreased the proliferation of HCC cells. Overexpression of miR-32 played an opposite role and attenuated the effects of overexpression of MT1JP. Therefore, MT1JP may upregulate PTEN by downregulating miR-32 to regulate HCC cell proliferation.

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

PurposeLenvatinib is a long-awaited alternative to Sorafenib for first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to Lenvatinib results in tumor progression and has become a major obstacle to improving the prognosis of HCC patients. Exploring the mechanisms underlying Lenvatinib resistance is considered essential for the treatment of advanced HCC.MethodsLenvatinib resistant HCC (LR-HCC) cells were generated and potential long non-coding RNAs (Lnc-RNAs) upregulated in LR-HCC cells were identified by RNA sequencing. The effects of upregulated Lnc-RNAs were evaluated in vitro in cell models and in vivo in experimental animals using quantitative cell viability and apoptosis assays.ResultsWe found that Lnc-RNA MT1JP (MT1JP) was upregulated in LR-HCC cells and inhibited the apoptosis signaling pathway. In addition, we found that sponging of microRNA-24-3p by MT1JP released Bcl-2 like 2 (BCL2L2), an anti-apoptotic protein, thereby forming a positive-feedback loop. The role of this feedback loop was validated using rescue assays. Additionally, we found that upregulation of MT1JP and BCL2L2 impaired the sensitivity of HCC cells to Lenvatinib both vitro and vivo.ConclusionsOur results suggest a novel molecular feedback loop between MT1JP and apoptosis signaling in Lenvatinib sensitive HCC cells.

C-myc promotes miR-92a-2-5p transcription in rat ovarian granulosa cells after cadmium exposure

Cadmium (Cd) can induce ovarian injury by microRNAs (miRNAs), however, the molecular mechanism of miRNAs after Cd exposure have not known. In this study, 56-day-old adult female Sprague-Dawley (SD) rats were injection with PMSG, after 48 h, ovarian granulosa cells (GCs) were extracted and cultured for 24 h, then treated with 0, 2.5, 5, 10 and 20 μM Cd for 24 h. The results showed that expression levels of miR-92a-2-5p (upregulated) and Bcl2 (downregulated) changed significantly after Cd exposure. The messenger RNA (mRNA) and protein expression levels of DNMT1, DNMT3A, and DNMT3B had changed, but no obvious differences were found in miR-92a-2-5p single site methylation. The transcription factors C-MYC (upregulated), E2F1 (downregulated), and SP1 (downregulated), which target miRNAs significantly changed after exposure to Cd. The human ovarian GC tumor line (COV434) was used to knocked down C-myc, and the expression of miR-92a-2-5p was downregulated in the COV434-C-myc + 10 μM Cd group compared with COV434 cells. The N6-methyladenosine (m6A) methylation modification levels of long noncoding RNA (lncRNA) MT1JP and lncRNA CDKN2B-AS, which regulate miR-92a-2-5p were detected. In the 10 μM Cd group, m6A methylation levels at MT1JP-84, CDKN2B-AS-257, and CDKN2B-AS-329 were reduced. In summary, after Cd exposure, expression of miR-92a-2-5p, which targets the antiapoptotic gene Bcl2, was upregulated, which may be primarily related to upregulation of C-myc. MiR-92a-2-5p promoter DNA methylation may has no obvious effect on miR-92a-2-5p. Otherwise, the role of m6A methylation modified lncRNA MT1JP and lncRNA CDKN2B-AS in the regulation of miR-92a-2-5p needs further study.

Long Noncoding RNA (lncRNA) MT1JP Suppresses Hepatocellular Carcinoma (HCC) in vitro.

IntroductionThe purpose of this study was to evaluate the effects and mechanisms of the long noncoding RNA (lncRNA) MT1JP on hepatocellular carcinoma (HCC) in vitro.Patients and MethodsThirty pairs of tumor and adjacent normal tissues were collected from HCC patients. Tissue pathology and MT1JP expression were evaluated by hematoxylin and eosin staining and in situ hybridization (ISH), respectively. The correlation between MT1JP and HCC prognosis was investigated. MTT assays, cloning, flow cytometry, transwell assays, and wound-healing assays were used to evaluate the effects of MT1JP on HCC cell lines. RT-qPCR and Western blot were used to measure the relative mRNA and protein expression levels.ResultsThe expression of MT1JP was downregulated in HCC tumor tissues compared with that in adjacent normal tissues, while the percent survival was significantly greater in the high MT1JP expression group than in the low MT1JP expression group (P=0.0238). In vitro, overexpression of MT1JP suppressed the proliferation, invasion, and migration, reduced colony cell number, increased cell apoptosis, and induced G1-phase cell cycle arrest in Bel-7402 and Huh-7 cells. Meanwhile, the mRNA and protein expression levels of RUNX3 and P21 were significantly upregulated, whereas those of MMP2 and MMP9 were significantly downregulated, in Bel-7402 and Huh-7 cells overexpressing MT1JP (all P<0.001).ConclusionLncRNA MT1JP may function as a tumor suppressor in HCC. Overexpression of MT1JP suppressed HCC cell biological activities through the regulation of RUNX3.

LncRNA MT1JP inhibits the malignant progression of hepatocellular carcinoma through regulating AKT.

The purpose of this study was to investigate the expression profile of long non-coding RNA (lncRNA) MT1JP in hepatocellular carcinoma (HCC), and to explore the relationship between its expression level and the clinical indicators, as well as the prognosis of HCC patients. In this study, the expression level of MT1JP in 45 pairs of tumor tissue specimens and paracancerous ones collected from HCC patients were examined through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) method, and the interplay between MT1JP expression and clinical indicators, as well as the prognosis of HCC patients, was also analyzed. Meanwhile, the expression of MT1JP in HCC cell lines was further verified by qRT-PCR. In addition, MT1JP overexpression model was constructed using lentivirus in HCC cell lines (Hub7 and HepG2), and then, Cell Counting Kit-8 (CCK-8), cell colony formation assay, and flow cytometry were performed to examine the impact of MT1JP on the HCC cell functions. Additionally, whether MT1JP exerts its biological characteristics through protein kinase B (AKT) was finally explored. In this experiment, qRT-PCR results showed that the expression level of lncRNA MT1JP in tumor tissues of HCC patients was remarkably lower than that in adjacent tissues, and the difference was statistically significant. Meanwhile, compared with patients with high expression of MT1JP, patients with low expression of MT1JP had a higher pathological staging and a lower overall survival rate. In addition, overexpression of MT1JP remarkably attenuated the proliferation ability of HCC cells but enhanced cell apoptosis rate at the same time. Finally, Western blot results revealed that the overexpression of MT1JP may markedly reduce the AKT expression, thereby suppressing the malignant progression of HCC. LncRNA MT1JP expression is remarkably decreased in HCC tumor tissue samples, which is associated with pathological stage and poor prognosis of HCC patients. In addition, MT1JP may inhibit the malignant progression of HCC by downregulating AKT.

&lt;p&gt;Overexpression of lncRNA MT1JP Mediates Apoptosis and Migration of Hepatocellular Carcinoma Cells by Regulating miR-24-3p&lt;/p&gt;

ObjectiveThis study aimed to determine the effects of the long non-coding (lnc) RNA MT1JP on the apoptosis and migration of hepatocellular carcinoma cells.Patients and MethodsPatients with liver cancer admitted to the Second People’s Hospital of Liaocheng were included in this study. We transfected hepatocellular carcinoma cells with MT1JP and miR-24-3p and assessed their expression and effects on apoptosis and migration. Correlations were verified using a dual-luciferase reporter and RNA-binding protein coimmunoprecipitation.ResultsThe expression of MT1JP was downregulated (P < 0.05), whereas that of miR-24-3p was upregulated in liver cancer. Serum MT1JP levels were correlated with tumor size, alpha-fetoprotein (AFP), TNM stage, differentiation, and lymph node metastasis. Both MT1JP overexpression and miR-24-3p inhibition inhibited cellular proliferation and migration and increased apoptosis rates. They significantly downregulated expression of the cell migration-associated proteins matrix metalloproteinase -2, -9 (MMP-2, MMP-9) (P < 0.05). They upregulated the expression of Bcl-2-related X protein (Bax) and cysteinyl aspartate-specific proteinases (Caspase-3 and -9) proteins that are involved in apoptosis. They decreased expression of B-cell lymphoma/leukemia-2 (Bcl-2; P < 0.05). A target relationship between MT1JP and miR-24-3p was identified using dual-luciferase gene reporter assays and RNA-binding protein coimmunoprecipitations. MT1JP overexpression significantly downregulated miR-24-3p expression (P < 0.05). MT1JP and miR-24-3p expression were negatively correlated in liver cancer tissues (r = −0.561, P < 0.001; Pearson χ2 tests). Rescue experiments showed that upregulating miR-24-3p expression could counteract MT1JP overexpression in hepatocellular carcinoma cells.ConclusionMT1JP, even when expressed at low levels, participates in the proliferation, apoptosis, and migration of liver cancer cells by regulating miR-24-3p.

LncRNA MT1JP Suppresses Biological Activities of Breast Cancer Cells in vitro and in vivo by Regulating the miRNA-214/RUNX3 Axis.

IntroductionThe purpose of our research was to evaluate MT1JP in breast cancer.Material and MethodsFor clinical purpose, tissues were collected, and a correlation analysis ofMT1JP and miRNA-214 gene expressions was conducted. Using an in vitro study, MDA-MB-231 and MCF-7 cell lines were used as research objects in our research. Colony, flow cytometry, TUNEL, transwell, adhesion and wound healing assay were used to discuss the biological activities of the cells. In an in vivo study, tumor weight and volume were measured, and cell apoptosis was measured by TUNEL assay. The relative mechanism’s proteins were evaluated by Western blotting or immunohistochemistry assay.ResultsCompared with adjacent tissues, MT1JP and miRNA-214 gene expressions were significantly different (P<0.001, respectively). By in vitro and in vivo studies, the biological activities of the cells were significantly decreased in MDA-MB-231 and MCF-7 cell lines with MT1JP overexpression. The relative mechanism was correlated with miRNA-214/RUNX3 axis.ConclusionThe overexpression of MT1JP suppresses the biological activities of breast cancer cells by regulation miRNA-214/RUNX3 axis in vitro and vivo study.

Long Noncoding MT1JP Enhanced the Inhibitory Effects of miR-646 on FGF2 in Osteosarcoma.

Background: It has been reported that long noncoding RNA (lncRNA) MT1JP played a tumor-suppressive role in the development of many organs, such as liver and lung, but the exact mechanism is still unknown. In addition, the involvement of MT1JP in osteosarcoma (OS) and its clinical values are unknown. In this study, the authors explored the interactions among lncRNA MT1JP, miR-646, and FOXK1 in OS. Materials and Methods: Expression levels of MT1JP in both tumor and nontumor tissues from 42 early stage OS patients were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Plasma levels of MT1JP in both OS patients (n = 42) and healthy controls (n = 42) were also measured by RT-qPCR. ROC curve as used for diagnostic analysis. Overexpression experiments were performed to analyze the interaction among MT1JP, miR-646, and FGF2. Cell invasion and migration were analyzed by Transwell assays. Results: The authors found that MT1JP was significantly downregulated in OS tissues than in adjacent noncancer tissues. In addition, plasma MT1JP was also downregulated in OS patients than in healthy controls. The lower plasma levels of MT1JP in OS patients distinguished early stage OS patients from healthy controls. miR-646 was positive, but FGF2 was negatively correlated with MT1JP across OS tissues. The MT1JP overexpression upregulated miR-646 and downregulated FGF2, while the miR-646 overexpression downregulated FGF2, but showed no significant effects on the MT1JP expression. MT1JP and miR-646 overexpression inhibited the migration and invasion of OS cells. The FGF2 overexpression played the opposite role and attenuated the effects of MT1JP and miR-646 overexpression. Conclusions: In conclusion, MT1JP might downregulate FGF2 through miR-646 to inhibit OS cell migration and invasion. The downregulation of plasma circulating MT1JP may serve as an early diagnostic biomarker for OS.

LncRNA Metallothionein 1J Pseudogene Positively Regulate miRNA-383 to Suppress Osteosarcoma Biological Activities via Wnt Pathway

Background: Osteosarcoma is a type of primary bone tumor that usually occurs in the metaphyseal region of long bones. It has been unclear lncRNA MT1JP in osteosarcoma development. Material and Methods: The MG63 cell were respectively MT1JP, miRNA-383 and miRNA-383 inhibitor. Measuring the cell proliferation, apoptosis and cell cycle by MTT and flow cytometry and evaluation the MG63 cell invasion and migration by transwell and wound healing assay in difference groups. The relative proteins (Wnt, β-catenin, Cyclin D1, MMP-2 and MMP-9) were measured by Western blot (WB) assay. By luciferase target assay, analysis the correlation between miRNA-383 and Wnt in MG63 cell. Results: Compared with WT group, the cell proliferation rate of pcDNAMT1JP and miRNA-383 groups were significantly down-regulation with cell apoptosis rates and G1 phase rates were significantly increased (P &lt; 0.01, respectively). By transwell and wound healing assay, the invasion cell number and wound healing rate of pcDNA-MT1JP and miRNA-383 groups were significantly depressed (P &lt; 0.01, respectively). By WB assay, Wnt, β-catenin, c-Myc, MMP-2 and MMP-9 proteins expressions of pcDNA-MT1JP and miRNA-383 groups were significantly suppressed compared with those of WT group (P &lt; 0.01, respectively). By luciferase target assay, Wnt was the targeted gene of miRNA-383 in MG63 cell. Conclusion: MT1JP could suppress osteosarcoma cell lines MG63 cell biological activities via stimulating miRNA-383 and depressing Wnt pathway.

Long-Chain Non-Coding RNA (lncRNA) MT1JP Suppresses Biological Activities of Lung Cancer by Regulating miRNA-423-3p/Bim Axis.

BackgroundThis study aimed to explain the effects and mechanism of MT1JP in lung cancer development and treatment.Material/MethodsThirty non-small cell lung cancer (NSCLC) (stages I–II, 17 cases; stages III–IV, 13 cases) and adjacent normal tissues were obtained. MT1JP and miRNA-423-3p levels were assessed by in situ hybridization and Bim protein expression by immunohistochemistry, and the correlations determined were analyzed. Cell proliferation was determined using MTT and colony formation assay, and cell apoptosis was measured using flow cytometry. A549 cell invasion and migration were assessed by Transwell migration and scratch wound healing assays. Relative mRNA and protein expressions were assessed using real-time polymerase chain reaction and western blotting. Correlations between miRNA-423-3p and Bim protein were investigated using luciferase activity assay, and Bim protein expression was evaluated using western blotting.ResultsMT1JP, miRNA-423-3p, and Bim expressions in NSCLC cancer tissues and those in adjacent cancer tissues were significantly different (P<0.01 or P<0.001) with increasing stage. Compared with those in the normal control (NC) group, cell proliferation rates were significantly suppressed (P<0.01 or P<0.001) and cell apoptosis rates significantly increased (P<0.01 or P<0.001) in the miRNA inhibitor and lncRNA+miRNA inhibitor groups. Invasion cell numbers and wound healing rates were also significantly inhibited in the miRNA inhibitor and lncRNA+miRNA inhibitor groups (P<0.01 or P<0.001) compared with those in the NC group.ConclusionsThe lncRNA MT1JP suppresses NSCLC biological activities by regulating the miRNA-423-3p/Bim axis.

Long noncoding RNA MT1JP inhibits proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.

This study is carried out to elucidate the role of long noncoding RNAs (lncRNAs) MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells through the regulation of PTEN/Akt signaling pathway. The expression of MT1JP in 80 normal brain tissues and 138 glioma tissues, as well as glioma cell lines, was detected by quantitativereverse-transcription polymerase chain reaction. Besides, glioma cells with overexpression and low expression of MT1JP were constructed to confirm the role of MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells and the growth of glioma cells in vivo through the regulation of PTEN/Akt signaling pathway. MT1JP expression was downregulated in glioma tissues and cells. The low expression of MT1JP was considered as an independent risk factor for predicting overall survival in gliomas. After transfection of MT1JP overexpression plasmid, glioma cells showed decreased proliferation, migration and invasion ability, increased apoptosis rate, and decreased the tumorigenic ability of nude mice. The trends were opposite in glioma cells transfected with MT1JP poor expression plasmid. Collectively, our study suggests that lncRNA MT1JP is responsible for inhibiting proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.

Retracted: LncRNA MT1JP functions as a tumor suppressor via regulating miR-214-3p expression in bladder cancer.

Growing evidence suggested that the long noncoding RNAs (lncRNAs) regulate several pathophysiological processes in tumorigenesis and may be new biomarkers for tumor therapy. In this study, we studied the expression and role of lncRNA MT1JP in the development of bladder cancer. We demonstrated that the expression of MT1JP was downregulated in bladder tumor samples and cell lines. Ectopic expression of MT1JP suppressed cell proliferation, cycle, and invasion in bladder cancer. In addition, our result suggested that miR-214-3p overexpression decreased the luciferase activity of wild-type MT1JP but not mutated-type MT1JP and elevated expression of MT1JP decreased miR-214-3p expression in the bladder cancer cell. Furthermore, we indicated that the expression of miR-214-3p was upregulated in bladder tumor samples and cell lines. Ectopic expression of miR-214-3p promoted cell proliferation, cycle, and invasion in bladder cancer. MT1JP suppressed cell proliferation, cycle, and invasion via negative modulation of miR-214-3p in bladder cancer. These data suggested that lncRNA MT1JP acts a tumor suppressor gene in bladder cancer progression, considering MT1JP as a new therapeutic target in bladder cancer.

LncRNA MT1JP acts as a tumor inhibitor via reciprocally regulating Wnt/β-Catenin pathway in retinoblastoma.

The aim of this study was to investigate the roles of MT1JP and β-catenin in retinoblastoma. We performed quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) to quantify the expressions of MT1JP and β-catenin in 44 retinoblastoma tissues and matched non-tumor tissues. What's more, retinoblastoma cell lines were transfected with pcDNA3.1-MT1JP, after which proliferation, cell cycle, apoptosis, and expression of β-catenin as well as its downstream targets were assayed. We also conducted TOP-Flash reporter assay to explore the activity of Wnt/β-catenin signaling pathway. The results revealed that MT1JP was down-regulated, while β-catenin was highly expressed in retinoblastoma cells. Meanwhile, the forced expression of MT1JP impaired the expression of the β-catenin protein and its downstream targets such as cyclin D1, c-myc. We demonstrated that MT1JP was a tumor suppressor by negatively modulating the activity of the Wnt/β-catenin signaling pathway in the development of retinoblastoma and might function as a prognostic biomarker and therapeutic target.

LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer

BackgroundEmerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained.MethodsLncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments.ResultsLncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis.ConclusionMT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

LncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate the p53 pathway

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play important roles in transcriptional regulation, whereas the extent to which the lncRNAs also function at the posttranscriptional level is less known. In the present study, we report a lncRNA named MT1JP which acts as a tumor suppressor through a posttranscriptional mechanism. We found that MT1JP is differentially expressed in tumor tissues by analyzing data from a customized microarray applied to 76 pairs of matched normal and cancer tissue samples. By associating with the RNA-binding protein TIAR, MT1JP enhanced the translation of the master transcription factor p53, thereby regulating a series of pathways involving p53, such as the cell cycle, apoptosis and proliferation. When MT1JP was down-regulated, the protein level of p53 declined, which in turn accelerated cell deterioration and tumor formation. Moreover, differential expression of MT1JP in cancerous and normal tissues suggests that it may be a promising prognostic marker and a therapeutic target. Taken together, we identified MT1JP as a critical factor in restraining cell transformation by modulating p53 translation through interactions with TIAR, and this finding is likely to shed new light on future investigations about posttranscriptional or translational effects of lncRNAs during cell transformation.