MicroRNAs (miRNAs) are differentially expressed in various cancers and act as oncogenes or tumor suppressors. MiR-383 has been characterized as a cancer suppressor in several cancers. However, the exact expression patterns of miR-383 and the precise molecular mechanisms underlying its role in ovarian cancer have not been investigated thoroughly. In this study, we found that the expression of miR-383 was significantly downregulated in ovarian cancer tissues and ovarian cancer cell lines. Ectopic expression of miR-383 remarkably suppressed the ovarian cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of ovarian cancer cells, while low expression of miR-383 exhibited the opposite effect. Bioinformatics analysis suggested LDHA as a novel target of miR-383, and miR-383 suppressed the expression level of LDHA mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-383 was negatively correlated with LDHA in ovarian cancer tissues. In addition, modulation of miR-383 expression could affect the aerobic glycolysis in the ovarian cancer cells. Furthermore, Silencing of LDHA counteracted the effects of miR-383 suppression, while its overexpression reversed tumor inhibitory effects of miR-383. In conclusion, our study demonstrated that miR-383 regulated LDHA expression in ovarian cancer cells, thereby stunting glycolysis, cell proliferation and invasion.
Background Plantamajoside (PMS), an active anti-inflammatory component and antioxidant derived from Herba Plantaginis , has been reported to exert a suppressive effect in liver cancer in vivo . In this study, we tested the effects of PMS on the metastatic 95D cell line. Methods 95D cells were characterized as most sensitive to PMS across several lung cancer cell lines. Cell viability within 24 h was tested with CCK-8. Different concentrations of PMS (0, 50, 100, and 200 µg/mL) and 5 µg/mL of cisplatin were established for later 24 h treatment. Relative mRNA and protein expression were assessed with PCR and Western blotting. Cell proliferation and stemness were indicated with colony and sphere formation. Cell metastasis was evaluated with wound healing and Transwell. Apoptotic cells and mitochondrial membrane potential were investigated with flow cytometry. Results CCK-8 assay showed PMS to inhibit the viability of 95D cells in a dose-dependent manner. PMS decreased colony formation and inhibited stemness in 95D cells. Invasion and migration were also inhibited. Moreover, PMS induced cell apoptosis, and decreased mitochondrial membrane potential. All of these effects were dose dependent. Interestingly, PMS treatment reduced the protein expression of p-p38 MAPK and p-AKT but not that of p38 MAPK and AKT. Conclusions PMS inhibited proliferation, stemness, and migration, and initiated apoptosis in 95D cells, possibly through p38 MAPK and AKT dephosphorylation and mitochondria dysfunction. These findings support the promise of PMS as a prodrug in lung cancer treatment.
Background This study aims to investigate the effect of miR-212-5p overexpression targeting suppressor of cytokine signaling 5 (SOCS5) on the malignant proliferation of liver cancer cells HepG2 and tumor formation in nude mice with transplanted tumors. Methods Luciferase reporter assay was used to detect the targeted relationship between miR-212-5p and SOCS5, and SOCS5 was overexpressed by the SOCS5 pcDNA vector. MiR-212-5p mimic and pc DNA-SOCS5 were transfected into liver cancer HepG2 cells alone or in combination, and the cells were randomly divided into four groups, the control group, mimic group, SOCS5 group and mimic + SOCS5 group for subsequent experiments. The orthotopic xenograft mouse models were established by using HepG2 cells in BALB/c athymic nude mice. Results The results showed that there was a direct targeting relationship between miR-212-5p and SOCS5. Compared with the control group, the clone formation rate, the levels of Ki67, and proliferating cell nuclear antigen (PCNA) protein in the mimic group were significantly lower (P<0.05), but the apoptosis rate was significantly higher (P<0.05). The ratio of Bax/Bcl-2, cleaved Caspase-3/Caspase-3, and cleaved Caspase-9/Caspase-9 was significantly higher (P<0.05), while the ratios of p-phosphatidylinositol 3 kinase (PI3K)/PI3K, p- Protein kinase B (AKT)/AKT, and p-mammalian target of rapamycin (mTOR)/mTOR were significantly reduced (P<0.05). In the SOCS5 group, the result was reversed. Interesting, In the mimic+SOCS5 group the clone formation rate, the protein levels of Ki67, and PCNA were significantly decreased (P<0.05) while the apoptosis rate was significantly increased (P<0.05). The ratio of Bax/Bcl-2, cleaved Caspase-3/Caspase-3, and cleaved Caspase-9/Caspase-9 was significantly increased (P<0.05). The ratios of p-PI3K/PI3K, p-Akt/AKT, and p-mTOR/mTOR were significantly reduced (P<0.05). In vivo, The level of miR-212-5p was significantly increased, with SOCS5 decreased (P<0.05). Furthermore, the number of Ki67 positive cells was significantly reduced (P<0.05), and the apoptosis rate increased significantly (P<0.05). Additionally, the ratio of p-PI3K/PI3K, P-AKT/AKT, P-mTOR/mTOR decreased significantly (P<0.05). Conclusions miR-212-5p overexpression down-regulated SOCS5 could inhibit the malignant proliferation of HCC cells HepG2 and tumor formation in nude mice with transplanted tumors.
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