Purpose: Genistein is a natural phytoestrogen with various antitumor effects. In recent years, some microRNAs (miRNA) in cancer cells have been reported to be regulated by genistein. Our study focused on exploring the mechanisms of miRNA upregulation to inhibit the epithelial mesenchymal transformation (EMT) and stemness of hepatocellular carcinoma (HCC). Patients and Methods: MiR-1275 was discovered by the transcriptome sequencing of miRNA expression profiles in HepG2 cells treated with genistein or DMSO as a control. Then, we performed series functional experiments in vitro and vivo to explore the relationship between genistein and miR-1275 in HCC. The target gene (Eukaryotic initiation factor 5A2, EIF5A2) of miR-1275 was predicted by databases and finally determined by a dual luciferase reporter assay. The downstream signaling pathway of EIF5A2 was assessed by bioinformatics analysis and Western blot. Results: the inhibition of genistein on the viability of HCC cells was enhanced by the increase in treatment time and dose, but it had no obvious inhibitory effect on normal hepatocytes (QSG-7701). Through qRT-PCR and transcriptome sequencing, we discovered that miR-1275 was lowly expressed in HCC, and it can be raised by genistein. The overall survival (OS) and recurrence-free survival (RFS) of HCC patients with lowly expressed miR-1275 were lower than those of those with high expression levels. In vitro and vivo experiments exhibited that genistein and the overexpression of miR-1275 can both significantly suppress the proliferation, migration, invasion, metastasis, EMT and stemness of HCC. Moreover, the inhibition can be further enhanced when miR-1275 mimic and genistein exist together. Finally, we demonstrated that miR-1275 can inhibit the epithelial mesenchymal transformation (EMT) and stemness of HCC via inhibiting the EIF5A2/PI3K/Akt pathway. Conclusion: Our findings proved that genistein can inhibit the EIF5A2/PI3K/Akt pathway by upregulating miR-1275 so as to attenuate the EMT and stemness of HCC cells to restrict their progression and metastasis.
Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent studies have demonstrated that lncRNAs play an important role in tumorigenesis. LINC01291 has been confirmed to be involved in the proliferation and migration of different cancers, although the function of LINC01291 in HCC is still unknown.Methods: First, the expression of LINC01291 in 50 paired HCC tissues, adjacent normal tissues and HCC cell lines was measured by a quantitative real-time polymerase chain reaction. Then, the function of LINC01291 in HCC cell proliferation, migration and invasion was measured by colony formation, Cell Counting Kit-8 assays, wound healing assays and transwell assays. In addition, E-cadherin, N-cadherin, vimentin and oxidative stress-responsive 1 (OXSR1) protein expression levels were assessed via western blotting. Luciferase reporter assays were used to confirm the relationship between LINC01291 and miR-186-5p, as well as miR-186-5p and OXSR1 mRNA.Rescue assays and in vivo experiments further confirmed the LINC01291/miR-186-5p/OXSR1 axis in the progression of HCC.Results: LINC01291 was upregulated in both HCC tissues and cell lines. Knockdown of LINC01291 inhibited the proliferation, migration, invasion and epithelialmesenchymal progression (EMT) of HCC cells. In addition, LINC01291 could overexpress OXSR1 by sponging miR-186-5p, and OXSR1 overexpression or miR-186-5p inhibition could rescue the effect of LINC01291 knockdown in YY-8103 cell lines. In addition, lentiviral sh-LINC01291 could effectively inhibit the growth of subcutaneous YY-8103 xenograft tumors, whereas the anticancer effect could be reversed by cotransfection with in-miR-186-5p or ov-OXSR1.Conclusions: LINC01291 can promote the proliferation, migration, invasion and EMT of HCC cells via the miR-186-5p/OXSR1 axis, and sh-LINC01291 can inhibit tumor growth in a xenograft mouse model. Highlights• LINC01291 is upregulated in HCC by database and a qRT-PCR.• LINC01291 can promote the development of HCC by regulating the miR-186-5p/OXSR1 axis.Jian Chu, Guangyong Geng and Xiaoming Ai contributed equally to this work.
Background: Long non-coding RNAs have been established to promote or inhibit the oncogenic and tumorigenic potential of various cancers, acting as competing endogenous RNAs (ceRNAs) for specific microRNAs. The primary objective of the study was to investigate the underlying mechanism by which the LINC02027/miR-625-3p/ PDLIM5 axis affects proliferation, migration and invasion in hepatocellular carcinoma (HCC). Methods:The differentially expressed gene was selected based on gene sequencing and bioinformation database analysis of HCC and adjacent non-tumor tissues. The expression of LINC02027 in HCC tissues and cells and its regulatory effect on the development of HCC were detected by colony formation, cell counting kit-8 assays, wound healing assays, Transwell assays and subcutaneous tumorigenesis assays in nude mice. According to the results of database prediction, quantitative real-time polymerase chain reaction and dual-luciferase reporter assay, the downstream microRNA and target gene were searched. Finally, HCC cells were transfected with lentivirus and used for cell function assays in vitro and in vivo.Results: Downregulation of LINC02027 was detected in HCC tissues and cell lines and was associated with poor prognosis. The overexpression of LINC02027 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, LINC02027 inhibited epithelial-to-mesenchymal transition. As a ceRNA, LINC02027 inhibited the malignant ability of HCC by competitively binding to miR-625-3p to regulate the expression of PDLIM5.
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