Circ_0007386 Promotes the Progression of Hepatocellular Carcinoma Through the miR-507/ CCNT2 Axis.

Background: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown. Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed. Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial-mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment. Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients.

MiR-507 inhibits the progression of gastric carcinoma via targeting CBX4-mediated activation of Wnt/B-catenin and HIF-1α pathways

Purpose: Gastric carcinoma (GC) is a common malignant disease with high morbidity and mortality. MiR-507 has been confirmed as a tumor inhibitor which can suppress the progression of multiple cancers while its role in GC remains unknown.MethodsIn this study, the expression levels of miR-507 in the GC tissues and cells were observed by qRT-PCR, and CCK-8 assay, transwell asssay and TUNEL assay were used to observe the function of miR-507 on GC. The miRNA database and dual-luciferase reporter assay were used to investigate the downstream target of miR-507. Moreover, the activities of Wnt/β-catenin and HIF-1α pathways were observed by western blot.ResultsThe results showed that miR-507 was significantly downregulated in GC tissues and cell lines, and miR-507 upregulation effectively inhibited the proliferation and invasion and induced the apoptosis of GC cells. CBX4 was a downstream target of miR-507, and CBX4 could reverse the effects of miR-507 on the GC cells. Moreover, it was determined that miR-507 could inhibit CBX4 expression to suppress the activation of Wnt/β-catenin and HIF-1α pathways.ConclusionsIn conclusion, it suggests that miR-507 could inhibit the progression of GC via regulating CBX4-mediated activation of Wnt/β-catenin and HIF-1α pathways. (AU)

MiR-507 inhibits the progression of gastric carcinoma via targeting CBX4-mediated activation of Wnt/ß-catenin and HIF-1α pathways.

PURPOSE: Gastric carcinoma (GC) is a common malignant disease with high morbidity and mortality. MiR-507 has been confirmed as a tumor inhibitor which can suppress the progression of multiple cancers while its role in GC remains unknown. METHODS: In this study, the expression levels of miR-507 in the GC tissues and cells were observed by qRT-PCR, and CCK-8 assay, transwell asssay and TUNEL assay were used to observe the function of miR-507 on GC. The miRNA database and dual-luciferase reporter assay were used to investigate the downstream target of miR-507. Moreover, the activities of Wnt/ß-catenin and HIF-1α pathways were observed by western blot. RESULTS: The results showed that miR-507 was significantly downregulated in GC tissues and cell lines, and miR-507 upregulation effectively inhibited the proliferation and invasion and induced the apoptosis of GC cells. CBX4 was a downstream target of miR-507, and CBX4 could reverse the effects of miR-507 on the GC cells. Moreover, it was determined that miR-507 could inhibit CBX4 expression to suppress the activation of Wnt/ß-catenin and HIF-1α pathways. CONCLUSIONS: In conclusion, it suggests that miR-507 could inhibit the progression of GC via regulating CBX4-mediated activation of Wnt/ß-catenin and HIF-1α pathways.

Long non-coding RNA LINC00243 promotes proliferation and glycolysis in non-small cell lung cancer cells by positively regulating PDK4 through sponging miR-507.

Non-small cell lung cancer (NSCLC) is the main subtype of lung cancer. The overall survival of NSCLC patients is relatively low even after various treatments. Accumulating evidence demonstrated that long non-coding RNA (LncRNA) plays crucial roles in different biological process. However, the role of a novel LncRNA, LINC00243, in NSCLC remains unclear. We aimed to explore the biological role of LINC00243 in NSCLC. The mRNA and protein levels were determined by real-time PCR and western blot, respectively. Cell viability in vitro was detected by Cell Counting Kit-8 (CCK-8) assay and colony-formation assay. Reporter assay was used to detect the interactions between molecules, and the interaction was assessed by RNA pull-down assay. LINC00243 expression increased in human NSCLC tissues and associated with poor prognosis of NSCLC patients. LINC00243 knockdown inhibited proliferation and glycolysis of NSCLC cells. Mechanically, LINC00243 acted as a molecular sponge for miR-507, and miR-507 reversed the effect of LINC00243 on promoting proliferation and glycolysis of NSCLC cells. Moreover, LINC00243 modulated expression of endogenous miR-507-targeted PDK4. LINC00243 promotes proliferation and glycolysis in NSCLC cells by positively regulating PDK4 through sponging miR-507. LINC00243 could be the potential target for NSCLC treatment clinically.

Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis.

BACKGROUND AND OBJECTIVES: This study aims to explore the effects of a long non-coding RNA, LINC00525, on colorectal cancer (CRC) and its underlying molecular mechanisms. METHODS: The qPCR, MTT, colony formation, Western blotting, Luciferase reporter and biotin pull-down, shRNA knockdown and DNA fragmentation assays were performed in this study. RESULTS: High expressions of LINC00525 were associated with poor prognosis of CRC patients. LINC00525 knockdown decreased stemness properties and increased sensitivities to oxaliplatin. MiR-507 was a direct target of LINC00525 and overexpression of miR-507 significantly decreased abilities of tumorsphere formation and cell growth. Overexpression of miR-507 resulted in a decrease of expression of cancer stem cell markers and the increase of apoptosis rates. MiR-507 regulated the expression of ELK3. In addition, LINC00525 knockdown decreased the expression of ELK3. Restoration of ELK3 expression abrogated the effects of LINC00525 knockdown. LINC00525 could be served as prognostic marker of CRC. CONCLUSIONS: LINC00525 enhanced stemness properties and increased sensitivities of CRC cells to oxaliplatin by targeting miR-507/ELK3 axis.

Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis

BACKGROUND AND OBJECTIVES: This study aims to explore the effects of a long non-coding RNA, LINC00525, on colorectal cancer (CRC) and its underlying molecular mechanisms. METHODS: The qPCR, MTT, colony formation, Western blotting, Luciferase reporter and biotin pull-down, shRNA knockdown and DNA fragmentation assays were performed in this study. RESULTS: High expressions of LINC00525 were associated with poor prognosis of CRC patients. LINC00525 knockdown decreased stemness properties and increased sensitivities to oxaliplatin. MiR-507 was a direct target of LINC00525 and overexpression of miR-507 significantly decreased abilities of tumorsphere formation and cell growth. Overexpression of miR-507 resulted in a decrease of expression of cancer stem cell markers and the increase of apoptosis rates. MiR-507 regulated the expression of ELK3. In addition, LINC00525 knockdown decreased the expression of ELK3. Restoration of ELK3 expression abrogated the effects of LINC00525 knockdown. LINC00525 could be served as prognostic marker of CRC. CONCLUSIONS: LINC00525 enhanced stemness properties and increased sensitivities of CRC cells to oxaliplatin by targeting miR-507/ELK3 axis.

LncRNA UCA1-miR-507-FOXM1 axis is involved in cell proliferation, invasion and G0/G1 cell cycle arrest in melanoma.

Recently, the incidence of melanoma has been on the rise. Patients with distant metastasis share poor prognosis. Increasing studies have been conducted to clarify the molecular mechanisms as well as to investigate potential effective therapeutic targets in the development of melanoma. This study focuses on the LncRNA UCA1 and its downstream regulated factors. In our experiments, UCA1 expression was discovered to be upregulated in melanoma tissues and cells, while the depletion of UCA1 led to the inhibition of cell proliferation, invasion and cell cycle arrest. To further our understanding of the mechanisms of UCA1, a system of experiments was built. We found that miR-507 could directly bind to UCA1 at the miRNA recognition site, and that there was a negative correlation between miR-507 and UCA1. Additionally, FOXM1 is a target of miR-507 and can be downregulated by either miR-507 overexpression or UCA1 depletion. Downregulated FOXM1 was analogous to the depletion of UCA1 and the overexpression of miR-507. These results, taken together, provide evidence for a novel UCA1 interaction regulatory network in tumorigenesis of melanoma.

MiR-507 inhibits the migration and invasion of human breastcancer cells through Flt-1 suppression.

Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase-1 (VEGFR-1/Flt-1) is a tyrosine kinase receptor that binds placental growth factor (PlGF). Flt-1 is also highly expressed in breast-cancer tissues and breast-cancer cell lines. However, the molecular mechanism by which Flt-1 promotes breast-cancer invasion and metastasis by binding to PlGF-1 is unclear. In this study, we discovered that PlGF-1 and Flt-1 played a key role in the migration and invasion of breast cancer. Flt-1 promoted the migration and chemotaxis of breast-cancer cells by binding to PlGF-1. In addition, Flt-1 was confirmed to be a direct target gene of miR-507. miR-507 up-regulation inhibited the invasion and metastasis of breast-cancer cells in vitro and in vivo. Flt-1 overexpression rescued the invasion partially caused by the ectopic expression of miR-507. miR-507 expression in breast-cancer tissues and cell lines was lower than that in adjacent non-neoplastic tissues and normal cells. Clinical analysis indicated that miR-507 was negatively correlated with tumor differentiation, lymphatic metastasis, and the expression of Flt-1 in breast cancer. Furthermore, we showed that miR-507 down-regulation was due to the hypermethylation of its promotor region. Our results indicated that miR-507 represented potential therapeutic targets in breast cancer by modulating Flt-1.

CCL5 promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-507 in human chondrosarcoma cells.

Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumor lymphangiogenesis and lymphatic metastasis. Chemokine CCL5 has been reported to facilitate angiogenesis and metastasis in chondrosarcoma. However, the effect of chemokine CCL5 on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has largely remained a mystery. In this study, we showed a clinical correlation between CCL5 and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that CCL5 promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium (CM) from CCL5-overexpressed cells significantly induced tube formation of human lymphatic endothelial cells (LECs). Mechanistic investigations showed that CCL5 activated VEGF-C-dependent lymphangiogenesis by down-regulating miR-507. Moreover, inhibiting CCL5 dramatically reduced VEGF-C and lymphangiogenesis in the chondrosarcoma xenograft animal model. Collectively, we document for the first time that CCL5 induces tumor lymphangiogenesis by the induction of VEGF-C in human cancer cells. Our present study reveals miR-507/VEGF-C signaling as a novel mechanism in CCL5-mediated tumor lymphangiogenesis. Targeting both CCL5 and VEGF-C pathways might serve as the potential therapeutic strategy to block cancer progression and metastasis in chondrosarcoma.