miR-328-3p overexpression attenuates the malignant proliferation and invasion of liver cancer via targeting Endoplasmic Reticulum Metallo Protease 1 to inhibit AKT phosphorylation

Abstract

Background: Liver cancer is one of the most common cancers worldwide. microRNAs (miRNAs) have been recognized as minimally invasive prognostic markers for distinct types of cancer. This study evaluates the mitigation role of miR-328-3p on liver cancer in vitro and in vivo.Methods: Liver cancer cell line Huh-7 and HepG2 were used for in vitro experiments. Compared with the control group, miR-328-3p overexpression inhibited the proliferation, invasion, and promoted apoptosis of Huh-7 cells. miR-328-3p and endoplasmic reticulum metalloprotease 1 (ERMP1) had an excellent targeting relationship. Compared with the pcDNA-ERMP1 transfection group, the ratios of p-PI3K/PI3K, p-AKT/ AKT, and p-mTOR/mTOR in miR-328-3p mimic and pcDNA-ERMP1 co-transfection group were significantly decreased. Animal models were set up using four-week-old immunodeficient BABL/c female nude mice. Huh-7 cells transfected with lentivirus holding miR-328-3p or empty vector were injected into the right dorsal side of BABL/c nude mice, respectively. Tumor volume was measured every five days.After one month, animals were sacrificed, xenograft tumors were dissected and weighed for RT-PCR and immunohistochemical assays.Results: Compared with control group, miR-328-3p overexpression significantly inhibited tumor weight (0.46±0.07 vs. 0.11±0.05 g, P<0.05) and tumor volume (1876±321 vs. 543±168 mm 3 , P<0.05) after thirty days. miR-328-3p overexpression significantly downregulated the percentage of Ki67 positive cells, N-cadherin positive cells and vimentin positive cells.Conclusions: These findings suggested that miR-328-3p could be a new treatment or a novel marker for liver cancer prognosis.

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

“…Zhang et al also showed downregulation of miR-328-3p in penile cancer tissues relative to adjacent non-cancerous tissues by Next-Generation Small RNA Sequencing [ 42 ]. MiRmiR-328-3p inhibits metastasis in colorectal cancer via inactivation of the PI3K/Akt signaling pathway [ 58 ] and reduces invasion as well as EMT in liver cancer via by targeting endoplasmatic reticulum metallo protease 1 ( ERMP1 ) to inhibit AKT phosphorylation [ 59 ].…”

CCL23 suppresses liver cancer progression through the CCR1/AKT/ESR1 feedback loop

“…Liu et al found Nrf2 could activate the AKT/p21 pathway, resulting in increased cell cycle progression of HCC cells 23 . Lu et al reported that miR‐328‐3p overexpression inhibited the PI3K/AKT pathway to attenuate the malignant proliferation and invasion of liver cancer 39 . A mechanism explaining the link between induction of AKT activation and concomitant repression of ERα activation is reported in breast cancer.…”

Subcellular Localization of miRNAs and Implications in Cellular Homeostasis

“…Additionally, ER-related miRNAs play a crucial role in cancer proliferation, metastasis and apoptosis. For example, the overexpression of miR-328-3p, targeting ER metalloprotease 1 (ERMP1), prevented liver cancer cell proliferation and invasion in female nude mice by reducing phosphorylation [92]. RT-qPCR analyses of biopsy specimens and cell lines verified that miR-370 is upregulated in gastric cancer, and Circ_002117 inhibits miR-370 to stimulate ER stress-induced apoptosis [93].…”