miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs

Abstract

BackgroundRecently, miR-10b is identified as a miRNA highly expressed in many human cancers, promoting cell migration and invasion. However, the specific function of miR-10b in hepatocellular carcinoma (HCC) is unclear at this point.MethodsThe miR-10b expression levels in 60 paired different TNM Stage HCC tumor tissues compared with adjacent non-tumor (ANT) tissues, normal tissue control (8 benign tumor and 7 normal liver tissues), 3 normal liver and 7 HCC cell lines were measured by real-time quantitative RT-PCR and to evaluate their association with HCC clinicopathologic features. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after transfection. The effect of miR-10b on HCC in vivo was validated by murine xenograft model.ResultsWe found that miR-10b expression was increased in human HCC tissues and cell lines compared with normal control, respectively. The expression of miR-10b was correlated with HCC metastatic ability. Overexpression of miR-10b in MHCC-97L cells increased cell motility and invasiveness, whereas inhibition of miR-10b in MHCC-97H cells reduced cell motility and invasiveness in vitro and in vivo. We also showed that HOXD10 was negatively regulated by miR-10b at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. Furthermore, we found that miR-10b induced HCC cell invasion and migration by modulating the HOXD10 target gene RhoC, uPAR, MMP-2 and MMP-9 expression.ConclusionsOur results suggested that miR-10b was overexpressed in HCC and promoted HCC cell migration and invasion through the HOXD10/ RhoC/ uPAR/ MMPs pathway which may provide a novel bio-target for HCC therapy.

MicroRNA-10b inhibits proliferation, migration and invasion in cervical cancer cells via direct targeting of insulin-like growth factor-1 receptor

“…Previously, miR-10b was revealed to be upregulated in numerous types of human cancers, including melanoma (30), gastric cancer (31), non-small-cell lung cancer (32), glioma (33), colorectal cancer (34), bladder cancer (35), breast cancer (36), nasopharyngeal carcinoma (37), pancreatic cancer (38) and hepatocellular carcinoma (39). In addition, miR-10b expression levels were revealed to be associated with clinicopathological factors.…”

“…Previous studies demonstrated that ectopic miR-10b expression improved migration and invasion abilities of bladder cancer, nasopharyngeal carcinoma and gastric cancer cells (31,35,37). Liao et al revealed that restoration of miR-10b expression enhanced proliferation, migration and invasion of hepatocellular carcinoma (39,43). In non-small-cell lung cancer, miR-10b overexpression prompted cell proliferation and invasion, and inhibited apoptosis (32,44).…”

“…These contradictory results may be explained by the imperfect complementarity of the interactions between miRNAs and target genes (47). Different cancers have different target genes of miR-10b, including Hoxd10 (31) in gastric cancer, E-cadherin (41) and Krüppel-like factor 4 (44) in non-small-cell lung cancer, ras homolog family member C (RhoC) (34) in colorectal cancer and RhoC, urokinase-type plasminogen activator receptor matrix metalloproteinases (39) and cell adhesion molecule 1 (43) in hepatocellular carcinoma. In the present study, IGF-1R was identified as a novel target gene of miR-10b in cervical cancer.…”

Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways

“…The first metastasis-regulating miRNA, miR-10b, was initially found to be expressed at elevated levels in metastatic cell lines and primary tumors from patients with metastatic breast cancer (5, 7). A growing body of evidence has demonstrated that miR-10b expression is also positively associated with high-grade malignancy or metastasis in other cancer types, such as pancreatic cancer (8-10), glioblastoma (11-14), bladder cancer (15), and liver cancer (16). In addition, lymph node metastases express higher levels of miR-10b than paired primary tumors in multiple cancer types (17).…”

MiR-10b Directly Targets ZEB1 and PIK3CA to Curb Adenomyotic Epithelial Cell Invasiveness via Upregulation of E-Cadherin and Inhibition of Akt Phosphorylation

“…Many miRNAs are implicated in tumor growth and metastasis [5]. Of these miRNAs, miR-10b is upregulated in a number of human cancers, promoting cancer cell migration and invasion [6][7][8][9][10]. However, miR-10b is found to be downregulated in endometrial cancers such as endometrial serous adenocarcinoma (ESA) and endometrioid endometrial carcinoma [11, overall survival in ESA [11].…”