The overexpression of miRNA-212-5p inhibited the malignant proliferation of liver cancer cells HepG2 and the tumor formation in nude mice with transplanted tumor through down-regulating SOCS5

Abstract

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.

SOCS5 knockdown suppresses metastasis of hepatocellular carcinoma by ameliorating HIF-1α-dependent mitochondrial damage

“…Previous research of our research group shows that SOCS5 plays an important role in promoting the progress of HCC, especially by enhancing HCC metastasis [ 14 ]. This is consistent with the research of some scholars [ 25 , 26 ]. Some scholars also proposed the tumor inhibition effect of SOCS5 in HCC [ 27 ].…”

miRNAs in pancreatic cancer progression and metastasis

“…Implanting mice with breast cancer cells that had CRISPR-knockout of both miRNAs led to significantly reduced tumour volume and improved overall survival indicating an oncogenic role for both miR-23b and miR-27b in breast cancer. On the other hand, another study in which mice received xenograft transplantation of liver cancer cells that were transfected with miR-212-5p mimics, were later found to have significantly smaller tumours compared to control [ 20 ]. This was through decreased cancer cell proliferation and increased apoptosis via directly inhibiting the suppressor of cytokine signalling 5 (SOCS5).…”

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

“…Downregulation of miR-27b-3p indirectly reverses the tumor growth process, but it also affects the chemical sensitivity of oral squamous cell carcinoma (OSCC) and enhances the sensitivity of OSCC cells to cisplatin (Han et al. 2020 ; Ma et al. 2020 ).…”