MiR-HCC2 Up-regulates BAMBI and ELMO1 Expression to Facilitate the Proliferation and EMT of Hepatocellular Carcinoma Cells.
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ABSTRACT:
SUBMITTER: Yi J
PROVIDER: S-EPMC6603416 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Long non-coding RNA MALAT1 (Metastasis-associated lung Adenocarcinoma transcript-1) has been demonstrated to play a critical role in the regulation of cancer progression and metastasis. However, little is known about MALAT1 in nasopharyngeal carcinoma (NPC) pathogenesis and progression. METHODS:Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of MALAT1, miR-124 and Capn4 mRNA in NPC cell lines. The protein level of Capn4 was examined by western blot analysis. Cell proliferation was detected by MTT assay, trypan blue exclusion method and colony formation analysis. Cell invasion was determined by transwell chamber assay. Expression of EMT-related proteins was detected by western blot. The potential targets of MALAT1 and miR-124 were verified by target prediction and luciferase reporter assay. RESULTS:MALAT1 and Capn4 were upregulated while miR-124 expression was downregulated in NPC cell lines. MALAT1 knockdown inhibited proliferation, invasion and EMT of NPC cells. Moreover, MALAT1 improved Capn4 expression by sponging miR-124. MALAT1 upregulation abated miR-124-induced repression on NPC cell proliferation, invasion and EMT. Furthermore, Capn4 overexpression reversed the inhibitory effect of MALAT1 silencing on proliferation, invasion and EMT of NPC cells. CONCLUSION:MALAT1 promoted proliferation, invasion and EMT of NPC cells through de-repressing Capn4 by sponging miR-124. The present study revealed a novel MALAT1/miR-124/Capn4 regulatory axis in NPC, contributing to a better understanding of the NPC pathogenesis and providing a promising therapeutic target for NPC therapy.
| S-EPMC5678686 | biostudies-literature
Project description:Rationale: The incidence of hepatocellular carcinoma is rising worldwide. It is predicted that nearly half of the early-stage hepatocellular carcinoma (E-HCC) patients will develop recurrence. Dysregulated pH, a hallmark of E-HCC, is correlated with poor prognosis. The acidic microenvironment has been shown to promote the release of exosomes, the membrane vesicles recognized as intercellular communicators associated with tumor progression, recurrence, and metastasis. We, therefore, aimed to identify exosomes induced by acidic microenvironment that may regulate E-HCC progression and to explore their mechanisms and clinical significance in E-HCCs. Methods: miRNA microarray analysis and LASSO logistic statistic model were used to identify the main functional exosomal miRNAs. Invasion and scratch assays were performed to examine the migration and invasion of HCC cells. Immunoblotting and immunofluorescence were employed to detect the epithelial-to-mesenchymal transition (EMT) in HCC cells. Chromatin immunoprecipitation (ChIP) was used to analyze the binding of HIF-1α and HIF-2α to promoter regions of miR-21 and miR-10b. Results: The acidic microenvironment in HCC was correlated with poor prognosis of patients. Exosomes from HCC cells cultured in the acidic medium could promote cell proliferation, migration, and invasion of recipient HCC cells. We identified miR-21 and miR-10b as the most important functional miRNAs in acidic HCC-derived exosomes. Also, the acidic microenvironment triggered the activation of HIF-1α and HIF-2α and stimulated exosomal miR-21 and miR-10b expression substantially promoting HCC cell proliferation, migration, and invasion both in vivo and in vitro. In E-HCC patients, serum exosomal miR-21 and miR-10b levels were associated with advanced tumor stage and HIF-1α and HIF-2α expression and were independent prognostic factors for disease-free survival of E-HCC patients. Most importantly, we developed a nano-drug to target exosomal miR-21 and/or miR-10b and examined its therapeutic effects against HCC in vivo. Conclusion: Our findings suggested that the exosomal miR-21 and miR-10b induced by acidic microenvironment in HCC promote cancer cell proliferation and metastasis and may serve as prognostic molecular markers and therapeutic targets for HCC.
| S-EPMC6485281 | biostudies-literature
Project description:ObjectivesHepatocellular carcinoma (HCC) is one of the most common cancers and is a significant leading cause of cancer-related deaths worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with cancer development and progression. However, up to now little has been known concerning the role of miR-709 in HCC.Materials and methodsReal-time RT-PCR was performed to detect expression of miR-709 in HCC cell lines and tissues. To further understand its role in HCC, we restored its expression in HepG2 cell line through transfection with miR-709 mimics or inhibitors. CCK-8 proliferation assay, migration assay and invasion assay were used to detect functional roles of miR-709. Luciferase assay and western blotting were performed to detect the target gene of miR-709.ResultsWe found that miR-709 was highly expressed in HCC tissues and in HCC cell lines by qRT-PCR. Re-expression of miR-709 in HCC cells remarkably promoted cell migration and invasiveness in vitro. Subsequent investigation revealed that glypican-5 (GPC5) was a direct and functional target of miR-709 in HCC cells where overexpression of miR-709 impaired GPC5-induced inhibition of proliferation and invasion. Finally, analysis of miR-709 and GPC5 levels in human HCC tissues revealed that miR-709 inversely correlated with GPC5 expression.ConclusionsThese results suggest that miR-709 may positively regulate invasion and metastasis of HCC through targeting GPC5.
| S-EPMC6495981 | biostudies-literature
Project description:ObjectiveCirc-centro-some/spindle pole-associated protein (CSPP1) has been confirmed to be characterized in diverse human malignancies and its ectopic expression may regulate tumor progression and development. However, in hepatocellular carcinoma (HCC), its biological role, clinical significance and molecular mechanism are still unclear.MethodsCirc-CSPP1 expression and its prognostic values in HCC tissues were detected by qRT-PCR or in situ hybridization (ISH), and enriched by using Rnase R. The functional experiments (Circ-CSPP1 was overexpressed or knocked down) were performed in HCC cells. The HCC cell growth was analyzed by CCK-8 assay, transwell, wound healing and colony formation assays. The interation between circ-CSPP1 and miR-577/miR-577 and cyclin E2 (CCNE2) were determined by dual luciferase assay or RNA binding protein immunoprecipitation (RIP) assay. The RNA fluorescence in situ hybridization (FISH) assay was used to detect the subcellular distribution. Finally, an in vivo nude mouse tumor model was constructed.ResultsIn HCC patients and cells, circ-CSPP1 was aberrantly expressed, and its upregulation predicted poor prognosis, and closely correlated with tumor size and TNM stage. Circ-CSPP1 resisted RnaseR digestion, indicating it is a circular RNA structure. Moreover, overexpression of circ-CSPP1 promoted HCC cell viability, colony formation, migration, and invasion in vitro. Knockdown of circ-CSPP1 showed contrary results. Circ-CSPP1 acts as a miR-577 sponge and positively regulated the target of miR-577, CCNE2. Besides, miR-577 inhibitor rescued the suppressive effects of circ-CSPP1 knockdown on HCC cell growth, whereas was completely reversed by silencing of CCNE2. Finally, the in vivo experiments confirmed that circ-CSPP1 knockdown regulated xenograft tumor volume and downregulated CCNE2, p-Rb, E2F1 and c-myc expression.ConclusionThese findings revealed that circ-CSPP1 contributed to HCC progression by positively regulating CCNE2 via miR-577, thus established its potential as new a prognostic and therapeutic marker for HCC patients.
| S-EPMC7260814 | biostudies-literature
Project description:BackgroundATAD2 is associated with many cellular processes, such as cell growth, migration and invasion. However, no studies have been conducted on the molecular biological function of the ATAD2 gene in hepatocellular carcinoma (HCC).MethodsThe protein and mRNA level expression of ATAD2 was examined in tissues and cell lines. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. ATAD2 knockdown was used to analyze cell proliferation and invasion. The upstream and downstream of ATAD2 was analyzed by RT2 Profiler™ PCR array and luciferasex fluorescence system.ResultsATAD2 was highly expressed in liver cancer samples and correlated with poor survival. High ATAD2 expression was positively correlated with metastasis (P = 0.005) and was an independent prognostic factor in HCC (P = 0.001). ATAD2 depletion by RNA interference reduced their capacity for invasion and proliferation and led to a G1 phase arrest in vitro. Further study revealed that miR-372 was an upstream target of ATAD2 as miR-372 was bound directly to its 3' untranslated region (3' UTR). In addition, ATAD2 knockdown was found to extremely up-regulate APC expression and down-regulate CTNNA1 at the mRNA level.ConclusionsThe findings demonstrated that miR-372 suppressed the expression of ATAD2, which was highly expressed in HCC and exerted a proto-oncogene effect in hepatic carcinogenesis. In conclusion, ATAD2 may promote HCC progression.
| S-EPMC4016509 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.
| S-EPMC3928300 | biostudies-literature
Project description:Deoxythymidilate kinase (DTYMK) has been identified as a putative oncogene associated with the incidence of hepatocellular carcinoma (HCC), but the mechanisms whereby it regulates this cancer type remain uncertain. The present study was therefore designed to explore the role of DTYMK in HCC and to evaluate the underlying molecular mechanisms. MiRNAs associated with DTYMK expression levels in HCC were identified through analyses of both clinical samples and publically available gene expression datasets. We then assessed the putative functions of DTYMK and miR-148b-3p in this oncogenic context through studies of HCC cells and a murine xenograft model system. Correlation analyses and in vitro experiments led us to confirm DTYMK as a target of miR-148b-3p. In addition, we assessed dTTP levels associated with the DTYMK pathway in HCC cells to understand the functional implications of our experimental findings. We found that HCC tissues and cells exhibited marked DTYMK upregulation and miR-148b-3p downregulation, with the expression levels of DTYMK and miR-148b-3p being negatively correlated with one another. The impact of overexpressing DTYMK in tumor cells was partially reversed upon cellular transfection with miR-148b-3p mimics, providing conclusive evidence that DTMYK is a target of this miRNA. Importantly, DTYMK-related dTTP levels were also impacted by miR-148b-3p mimic transfection. DTYMK is a key regulator of HCC progression, and its expression is suppressed by miR-148b-3p, suggesting that this miR-148b-3p/DTYMK regulatory axis may be amenable to therapeutic targeting in patients with HCC.
| S-EPMC8739515 | biostudies-literature
Project description:Liver cancer is now one of the most lethal and commonest cancers in the world, among which over 90% is hepatocellular carcinoma (HCC). Recent studies have confirmed long non-coding RNAs (lncRNAs) are implicated in carcinogenesis. It has been reported lncRNA LINC00668 serves as an oncogene in several cancers. However, the mechanism where LINC00668 regulates HCC is still unclear. qRT-PCR analysis was adopted to detect the expression of relative RNAs. Cytoplasmic and nuclear RNA fraction analysis was conducted to verify the underlying molecular mechanism. Cell colony formation was carried out to test cell colony formation ability and transwell assays were performed to testify cell migratory and invaded abilities. Relevant protein expression level was measured by Western blot assay. LINC00668 was significantly up-regulated in HCC tissues and cell lines. LINC00668 knockdown inhibited cell proliferative, migratory and invasion abilities and slowed down the epithelial-mesenchymal transition (EMT) process. Mechanistically, LINC00668 positively modulates the expression of YY1 by competitively binding to miR-532-5p. It was revealed that LINC00668 up-regulation accelerated cell proliferation and motility in HCC and suggested LINC00668 could be a potential therapeutic target for HCC.
| S-EPMC7214398 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely unknown. Actually, we found that AHSA1 was significantly upregulated in HCC tissues and cell lines and was notably correlated with the poor clinical characteristics and prognosis of HCC patients in this study. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated that AHSA1 promoted the proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) of HCC. Moreover, the mechanistic study indicated that AHSA1 recruited ERK1/2 and promoted the phosphorylation and inactivation of CALD1, while ERK1/2 phosphorylation inhibitor SCH772984 reversed the role of AHSA1 in the proliferation and EMT of HCC. Furthermore, we demonstrated that the knockdown of CALD1 reversed the inhibition of proliferation and EMT by knocking AHSA1 in HCC. We also illustrated a new molecular mechanism associated with AHSA1 in HCC that was independent of HSP90 and MEK1/2. In summary, AHSA1 may play an oncogenic role in HCC by regulating ERK/CALD1 axis and may serve as a novel therapeutic target for HCC.
| S-EPMC9562867 | biostudies-literature
Project description:NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion. Consequently, patients exhibiting high NEK2 expression had poorer prognosis. This was corroborated by our multivariate analysis that showed NEK2 to be an independent prognostic factor for HCC patient survival. Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. Tumor xenograft data from Balb/c nude mice demonstrated that HCC cells with high NEK2 expression formed larger tumors than those with low NEK2 expression. Finally, we showed that miR-486-5p suppressed NEK2 by directly binding to its transcript 3'UTR. We also demonstrated an inverse relationship between miR-486-5p and NEK2 expression in HCC patients. These findings suggest miR-486-5p negatively regulates NEK2, which is a critical prognostic indicator of HCC patient survival after liver transplantation.
| S-EPMC5581084 | biostudies-other