Overexpression of miRNA-21 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma Cells via Suppressing SMAD7

Abstract

Purpose: This study aimed to explore the molecular mechanism of microRNA-21 and smad family member 7 in hepatocellular carcinoma. Method: A total of 57 participants were divided into control group (healthy participants, n = 10) and hepatocellular carcinoma group (hepatocellular carcinoma patients, n = 37). The expression of microRNA-21 levels were first detected in these two groups. Cell transfection was performed on hepatoma cell lines, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay to reveal proliferation and invasion ability. Furthermore, the relation between microRNA-21 and smad family member 7 was revealed by luciferase reporter gene and RNA immunoprecipitation assay. Finally, a transplantation tumor model of breast cancer in mice was constructed. Results: The serum indicators including α-alanine aminotransferase, aspartate aminotransferase, and albumin were differentially expressed between hepatocellular carcinoma group and control group. Compared to the control group, there was a high expression of microRNA-21 in hepatocellular carcinoma group. Low expression of microRNA-21 inhibited the proliferation and invasion of HepG2.2.15 and Huh7-1.3 cells. Luciferase reporter gene and RNA innumoprecipitation assay showed that smad family member 7 was the target gene of microRNA-21. Moreover, mice model analysis showed that microRNA-21 might regulate the growth of the transplanted tumors in mice by targeting smad family member 7. Conclusion: The upregulated microRNA-21 might participate in the proliferation and migration in cells of hepatocellular carcinoma via suppression of smad family member 7. Furthermore, serum indicators such as alanine aminotransferase, aspartate aminotransferase, and albumin might be used as serum diagnostic markers for hepatocellular carcinoma.

RETRACTED: LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

“… 14 Numerous miRNAs such as miR-21, miR-141, miR-769-5p and miR-7-5p have been reported to be abnormally expressed in HCC and play an important role in modulating the proliferation, migration and invasion of HCC cells. 15 - 18 Several recent studies have suggested that lncRNAs, act as “molecular sponges” of miRNAs and can affect the target mRNA expression and ultimately interfere with the occurrence and development of diseases. 12 However, the relationship between lncRNA RHPN1-AS1 and miR-7-5p remains uninvestigated in HCC.…”

MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study

“…SMAD7, a member of SMAD family, is reported to be associated with the development of a variety of cancers. Recent studies have shown that SMAD7 is present in common malignancies and acts as a tumor suppressor, including lung cancer, liver cancer, gastric cancer, bladder cancer, triple negative breast cancer, and osteosarcoma [11,[23][24][25][26][27][28]. In CRC, reduced level of SMAD7 is found to be involved in the process of cancer growth as well as the process of EMT and invasion [29].…”

Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways

“…The most common genetic alteration activating PI3K is the genetic ablation of the tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K-AKT signaling (39). miR-21 is one of the most frequently observed abnormal miRNAs in human cancers and is one of the first miRNAs described as oncogenic ncRNA (40)(41)(42)(43)(44). A large-scale miRNA analysis of 540 samples from six different types of solid tumors showed that miR-21 is the only up-regulated miRNA in all cancer types (45).…”