MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2
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ABSTRACT: MicroRNAs (miRNAs) expression profiles are widely investigated in the major cancers, but their expression in patients plasmas of cancers have not yet to be fully elucidated. We investigated expression profiles of miRNAs in patients preoperative/postoperative plasmas of clear cell renal cell carcinomas (ccRCCs) by using a miRNAs microarray platform which covers a total of 1,523 human miRNAs.
Project description:BackgroundLipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been confirmed to participate in the pathological processes of cancers, including tumour occurrence and inhibition. However, the role and mechanism of miR-765 have not been elucidated in clear cell renal cell carcinoma (ccRCC).MethodsUsing The Cancer Genome Atlas (TCGA) database and qRT-PCR, we investigated differences in miR-765 and proteolipid protein 2 (PLP2) expression, as well as their clinical relevance. To investigate the function of miR-765 and PLP2 in ccRCC, we performed in vitro and in vivo experiments to explore their biological functions in ccRCC.FindingsIn this study, we showed that miR-765 was upregulated in the plasma of ccRCC patients after tumour resection. Consistently, ccRCC tissues had low expression of miR-765 when compared with corresponding non-cancerous tissues. Overexpression of miR-765 suppressed cell proliferation and metastasis in vitro and in vivo. Mechanistic studies demonstrated that PLP2 was a direct target gene of miR-765. PLP2 was highly expressed in ccRCC tissues, and high PLP2 levels were positively correlated with higher tumour stage and grade and poor prognosis. PLP2 expression was negatively correlated with the miR-765 level in patient samples. We further showed that PLP2 restrained the cell metastasis and proliferation induced by miR-765 and reduced the lipid-eliminating effects of miR-765 in renal cancer cells.InterpretationOur findings suggest that miR-765 may function as a tumour suppressor and eliminate lipids in clear cell renal cell carcinoma by targeting PLP2.FundingThis work was funded the grants from the National Natural Scientific Foundation of China (Grant No. 81672528, 81672524, 81602218, 31741032, 81902588).
Project description:MicroRNAs (miRNAs) expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. We investigated expression profiles of miRNAs in clear cell renal cell carcinomas (ccRCCs) and in matched normal kidney tissues (NCTs) by using a miRNAs microarray platform which covers a total of 851 human miRNAs.
Project description:MicroRNAs (miRNAs) expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. We investigated expression profiles of miRNAs in clear cell renal cell carcinomas (ccRCCs) and in matched normal kidney tissues (NCTs) by using a miRNAs microarray platform which covers a total of 851 human miRNAs. Tumor tissue samples were immediately snap-frozen in liquid nitrogen after surgery, and then stored in a deep freezer at -80°C. Total RNA was extracted from 5 ccRCC tissues and paired NCTs and expression profiles of miRNAs were screened by using a miRNA microarray platform.
Project description:MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis.
Project description:MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis
Project description:In this study, we investigated CNAs of 20 primary clear cell renal cell caricinomas (ccRCCs), 20 corresponding metastases and another subsets of 30 primary ccRCCs by 44k oligonucleotide-based array comparative genomic hybridization (array CGH). 20 primary ccRCCs, 20 corresponding metastases and another subsets of 30 primary ccRCCs.
Project description:Background: Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression. Aim: Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma. Materials and Methods: 149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data. Results: Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02). Conclusions: Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
Project description:BACKGROUND: Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). MicroRNAs (miRNAs) are small non-coding RNA-strands (~22 nucleotides) that post-transcriptionally regulate gene-expression. Studies have shown that miRNAs are potential diagnostic markers in other cancers; however, it is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMP. OBJECTIVE: To identify differentially expressed microRNAs which can aid in the diagnostics of MPM. METHODS: We screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed paraffin-embedded (FFPE) preoperative diagnostic biopsies, surgically resected MPM-specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP) from 5 patients. RESULTS: By comparing the change in microRNA expression in patient-matched tissue samples, we identify 14 miRNAs which exhibit statistically significant deregulation between sample groups. CONCLUSION: Based on this initial screening of miRNA expression, we have identified 14 miRNAs which are potential diagnostic biomarkers and may aid in diffferentiating RMP from MPM.