Qingping Jiang

Integrated microRNA and mRNA Transcriptome Sequencing Reveals the Potential Roles of miRNAs in Stage I Endometrioid Endometrial Carcinoma

Endometrioid endometrial carcinoma (EEC) is the most dominant subtype of endometrial cancer. Aberrant transcriptional regulation has been implicated in EEC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing in EEC to investigate potential molecular mechanisms underlying the pathogenesis. Total mRNA and small RNA were simultaneously sequenced by next generation sequencing technology for 3 pairs of stage I EEC and adjacent non-tumorous tissues. On average, 52,716,765 pair-end 100 bp mRNA reads and 1,669,602 single-end 50 bp miRNA reads were generated. Further analysis indicated that 7 miRNAs and 320 corresponding target genes were differentially expressed in the three stage I EEC patients. Six of all the seven differentially expressed miRNAs were targeting on eleven differentially expressed genes in the cell cycle pathway. Real-time quantitative PCR in sequencing samples and other independent 21 pairs of samples validated the miRNA-mRNA differential co-expression, which were involved in cell cycle pathway, in the stage I EEC. Thus, we confirmed the involvement of hsa-let-7c-5p and hsa-miR-99a-3p in EEC and firstly found dysregulation of hsa-miR-196a-5p, hsa-miR-328-3p, hsa-miR-337-3p, and hsa-miR-181c-3p in EEC. Moreover, synergistic regulations among these miRNAs were detected. Transcript sequence variants such as single nucleotide variant (SNV) and short insertions and deletions (Indels) were also characterized. Our results provide insights on dysregulated miRNA-mRNA co-expression and valuable resources on transcript variation in stage I EEC, which implies the new molecular mechanisms that underlying pathogenesis of stage I EEC and supplies opportunity for further in depth investigations.

CD20-positive NK/T-cell lymphoma with indolent clinical course: report of case and review of literature

AbstractCD20-positive T-cell lymphoma is extremely rare and only two cases of CD20-positive NK/T-cell lymphoma with aggressive clinical courses have been described in the literature. We present a case of unusual NK/T-cell lymphoma with CD20 expression in nasal cavity occurring in an elder female patient. The patient had presented with left nasal cavity nodule for 10 years. CT scan revealed a mass was located at the left anterior nasal cavity and was observed to extend into the ethmoid sinus. There was no regional lymph node involvement. Biopsy was performed and microscopical inspection revealed the lesion was composed of small- to middle-size atypical lymphoid cell, histiocytes, eosinophils, and neutrophils. The lymphoid cells were strongly immunoreactive to CD3, CD20, CD56, TIA-1 and granzyme-B. The Epstein-Barr virus genomes were also found in tumor cells by in situ hybridization. By genetic analysis, however, no clonal rearrangement of the T cell receptor-γ genes (TCRG), or the immunoglobulin heavy chain (IgH) gene was found. A diagnosis of CD20-positive extranodal NK/T-cell lymphoma, nasal type was made. The patient refused chemotherapy, and had been only on regular follow-up for 6 months. There was no sign of enlargement of tumor and extra-nasal dissemination by whole body positron emission tomography/computed tomography (PET/CT) study. The accurate diagnosis of NK/T-cell lymphoma with CD20 expression is important, but the indolent behavior of the present case is more unusual. A long-term follow-up is suggested to be performed to inspect the progression for this tumor.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1320848277788495

An extraordinary T/NK lymphoma, nasal type, occurring primarily in the prostate gland with unusual CD30 positivity: case report and review of the literature

Extranodal NK/T cell lymphoma(NKTCL), nasal type, occurring primarily in the prostate gland, is extremely rare. We present a case of primarily prostatic NKTCL in a 59-year-old man suffering from dysuria. Histological examinations revealed that diffused, large-sized, pleomorphic lymphocytes were arranged in an angiocentric distribution with large areas of geographic necroses. Additionally, the prostatic glands were diffusely infiltrated by heteromorphous lymphocytes forming lymphoepithelial lesions. The tumor cells were strongly expressed CD3ϵ, CD56, TIA-1, granzyme B and EBV-encoded RNAs. And interestingly, the lymphoid cells were also strongly immunoreactive with CD30. A rearrangement study showed T-cell receptor γ-chain gene rearrangement with monoclonal appearance. Though postoperative combination of chemotherapy was given, the patient died four months later. Our observation and other literatures indicate that extremely rare NKTCLs unusually express CD30. TCR gene rearrangement existed in some NKTCL, suggesting that a subset of NKTCL may be a mixed NK/T-cell differentiation.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9671878568932824.

A directly negative interaction of miR-203 and ZEB2 modulates tumor stemness and chemotherapy resistance in nasopharyngeal carcinoma

miR-203 is a tumor suppressor that is disregulated in numerous malignancies including nasopharyngeal carcinoma (NPC). However, the role of miR-203 in suppressing tumor stemness, chemotherapy resistance as well as its molecular mechanisms are unclear. In this study, we observed that miR-203 suppressed cell migration, invasion, tumor stemness, and chemotherapy resistance to cisplatin (DDP) in vitro and in vivo. miR-203 exerted these effects by targeting ZEB2 and downstream epithelial-mesenchymal transition (EMT) and tumor stemness signals. Interestingly we observed that miR-203 expression was directly suppressed by ZEB2 via targeting its promoter, which significantly reduced cell migration, invasion, tumor stemness, and chemotherapy resistance in NPC cells. Finally, we found that miR-203 was negatively correlated with ZEB2 expression in NPC tissues and tumor spheres. Our data demonstrate a directly negative feedback loop between miR-203 and ZEB2 participating in tumor stemness and chemotherapy resistance, highlighting the therapeutic potential of targeting this signal for NPC chemotherapy.

Identification and Validation of Potential Biomarkers for the Detection of Dysregulated microRNA by qPCR in Patients with Colorectal Adenocarcinoma

Colorectal cancer represents a lethal disease that has raised concern and has attracted significant attention. Adenocarcinoma is the most common type of colorectal cancer (CRC). MicroRNAs are thought to be potential biomarkers of CRC. Many researchers have focused on the expression pattern of miRNAs in CRC. However, previous studies did not pay particular attention to the effects of the degree of differentiation of the cancer with respect to the miRNA expression profile. First, this study compared the expression level of 1547 miRNAs by qRT-PCR in Colorectal adenocarcinoma tissues to that in paired normal tissues. In all, 93 miRNAs were identified that were significantly dysregulated in Colorectal adenocarcinoma relative to normal tissues (P<0.05). Then, we analyzed their potential as cancer biomarkers by ROC analysis, and the result revealed that three miRNAs with high sensitivity and specificity are suitable as biomarkers for the diagnosis of CRC (the value of the AUC was greater than 0.7). Interestingly, previous reports of 23 of these miRNAs have been scarce. Furthermore, we wanted to analyze the difference between well- and moderately differentiated cancers, and as expected, 58 miRNAs showed significant dysregulation. Importantly, 32 miRNAs were able to not only distinguish cancer tissues from normal tissues, but they were also able to identify well- and moderately differentiated cancers. In conclusion, the degree of differentiation has an important influence on the miRNA expression pattern. To avoid misdiagnoses and missed diagnoses, tumors of different degrees of differentiation should be treated differently when miRNAs are used as cancer biomarkers.

miR-16 induction after CDK4 knockdown is mediated by c-Myc suppression and inhibits cell growth as well as sensitizes nasopharyngeal carcinoma cells to chemotherapy

Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a negative automodulatory feedback loop between CDK4 and miR-16 that regulates cell cycle progression in nasopharyngeal carcinoma (NPC). By miRNA array and real-time PCR, we identified upregulation of tumor suppressor miR-16a, which inhibited cell cycle progression and sensitized NPC cells to chemotherapy. CDK4 knockdown reduced the expression of c-Myc, the latter of which directly suppresses the miR-16 expression by directly binding to the miR-16 promoter. Moreover, we found that miR-16 upregulation could reduce CDK4 expression by repressing CCND1 and thus forms a feedback loop via the CDK4/c-Myc/miR-16/CCND1 pathway. Finally, miR-16 was negatively correlated with CDK4 expression in NPC biopsies. In summary, our results define a double-negative feedback loop involving CDK4 and miR-16 mediated by c-Myc that modulates NPC cell growth and chemotherapy sensitivity.

CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma

BackgroundIn previous investigation, we reported that stably knocking down cyclin-dependent kinase 4(CDK4) induced expression of let-7c, which further suppressed cell cycle transition and cell growth by modulating cell cycle signaling in nasopharyngeal carcinoma (NPC). In this study, we further explored the molecular function and mechanism of CDK4 modulating miRNAs to stimulate cell cycle transition, cell growth, and Cisplatin (DDP) -resistance on in NPC.MethodsWe identified changes in miRNAs by miRNA array and real-time PCR and the effect on DDP after knocking down CDK4 in NPC cells. Further, we investigated the molecular mechanisms by which CDK4 modulated miR-15a in NPC. Moreover, we also explored the role of miR-15a and the effect on DDP in NPC. Finally, we analyzed the correlation of miR-15a and CDK4 expression in NPC tissues.ResultsIn addition to let-7 family members, we observed that upregulated expression of miR-15a was significantly induced in CDK4-suppressed NPC cells. Further, we found that knocking down CDK4 suppressed c-Myc expression, and the latter directly suppressed the expression of miR-15a in NPC. Furthermore, miR-15a as a tumor suppressor antagonized CDK4 repressing cell cycle progression and cell growth in vitro and in vivo and induced the sensitivity of cells to DDP by regulating the c-Myc/CCND1/CDK4/E2F1 pathway in NPC. Finally, miR-15a was negatively weak correlated with the expression of CDK4 in NPC.ConclusionsOur studies demonstrate that CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in NPC.

Decreased P27 protein expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma

BackgroundTo determine the correlation of cyclin-dependent kinase inhibitor 1B (p27) expression with clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient prognosis.MethodsReal-time PCR and immunohistochemistry were used to examine the mRNA and protein expressions of p27 in NPC and nasopharyngeal tissues. The relationship of p27 expression levels with clinical features and prognosis of NPC patients was analyzed.ResultsThe expression level of p27 mRNA was markedly lower in NPC tissues than that in the nasopharyngeal tissues (P = 0.0006). Specific p27 protein staining by immunohistochemistry was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells but decreased expression was observed in NPC samples compared to normal epithelium samples (P = 0.002). In addition, low levels of p27 protein were inversely correlated with the status of T classification (p = 0.002) and clinical stage (p = 0.019) of NPC patients. Patients with lower p27 expression had a significantly shorter overall survival time than did patients with high p27 expression. Multivariate analysis suggested that the level of p27 expression was not an independent prognostic indicator (p = 0.682) for NPC survival.ConclusionLow level of p27 expression is a potential unfavorable prognostic factor for patients with NPC.Virtual slidesThe virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1915282782109343.

MicroRNA-183 induces epithelial-mesenchymal transition and promotes endometrial cancer cell migration and invasion in by targeting CPEB1

The aim of this study is to evaluate the ability of microRNA‐183 (miR‐183) to influence epithelial‐mesenchymal transition (EMT) and cell proliferation, migration, invasion, and apoptosis in endometrial cancer (EC) by targeting cytoplasmic polyadenylation element binding protein 1(CPEB1). EC tissues with matched nonmalignant tissues were collected from 208 EC patients. Ishikawa and RL95‐2 cells were selected for cell experiments in vitro and each kind of cells were grouped into blank, negative control (NC), miR‐183 mimic, miR‐183 inhibitor, CPEB1 overexpression, and miR‐183 mimic + CPEB1 overexpression groups. Expressions of miR‐183, CPEB1, E‐cadherin, and Vimentin were determined by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blotting. Cell viability, colony formation ability, migration, invasion, and apoptosis were assessed by MTT assay, clone formation assay, scratch test, Transwell assay, and flow cytometry. In vivo tumorigenesis of Ishikawa cells was evaluated by tumor formation in nude mice. The miR‐183 expression was higher, but the CPEB1 expression was lower in EC tissues than in adjacent nonmalignant tissues. CPEB1 was confirmed as the target of miR‐183 by dual‐luciferase reporter assay. The miR‐183 mimic group had increased cell viability, colony formation ability, cell invasion and migration, tumor volume and weight in nude mice, but decreased cell apoptosis when compared with the blank group. The expression of E‐cadherin was down‐regulate, but expression of Vimentin was up‐regulate in the miR‐183 mimic group in comparison with the blank group. In terms of a comparison between the blank group and CPEB1 overexpression group, the CPEB1 overexpression group had suppressed cell viability, colony formation ability, cell invasion and migration, tumor volume and weight, but increased cell apoptosis. The expression of E‐cadherin was up‐regulated, but the expression of Vimentin was down‐regulated in the CPEB1 overexpression group in comparison with the blank group. The miR‐183 mimic + CPEB1 overexpression group had higher miR‐183 expression than the blank group. These findings indicate that miR‐183 induces EMT, inhibits apoptosis, and promotes cell proliferation, migration, invasion, and in vivo tumorigenesis in EC by targeting CPEB1.

Recovery from Talaromyces marneffei involving the kidney in a renal transplant recipient: A case report and literature review

Talaromyces marneffei is an emerging opportunistic infection among immunocompromised patients. We observe the first native case of disseminated T. marneffei involving the kidney in a renal transplant recipient in mainland China. We describe the comprehensive clinical course, and ultrasound imaging of renal transplant biopsy, pathologic images, and electron microscopy observation of the biopsy specimen, highlighting the relevance of biopsy findings and the blood culture. We also focus on the treatment and good outcome of the patient. Then we review the literature and show the additional 10 reported cases of T. marneffei in renal transplant recipients. In addition, we discuss the new methods of rapid diagnosis of T. marneffei. In brief, timely diagnosis and proper treatment of T. marneffei infection is important in renal transplant recipients.