miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells

Abstract

Background:The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC.Methods:MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines).Results:In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and β-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1.Conclusions:MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.

Candidate diagnostic miRNAs that can detect cancer in prostate biopsy

“…Many miRNAs identified as dysregulated in the present study have also been reported as altered in other cancer types, including breast cancer (miR‐374b‐5p, miR‐429, miR‐200b‐5p, miR‐200b‐3p, miR‐187‐3p, miR‐196a‐5p, miR‐183‐5p, miR‐21‐5p, and miR‐182‐5p); gastric cancer (miR‐374b‐5p, miR‐200c‐3p, miR‐18b‐5p, miR‐196a‐5p, miR‐21‐5p, and miR‐20a‐3p); ovarian cancer (miR‐141‐5p, miR‐182‐5p, miR‐483‐3p, and miR‐200c‐3p); hepatocellular carcinoma (miR‐135a‐5p, miR‐187‐3p, miR‐148a‐5p, miR‐200a‐3p, and miR‐9‐3p); colorectal cancer (miR‐9‐3p, miR‐135a‐5p, miR‐200c‐3p, miR‐200b‐3p, and miR‐182‐5p); thyroid cancer (miR‐7‐5p and miR‐9‐3p); lung cancer (miR‐200b‐5p, miR‐200b‐3p, miR‐9‐5p, miR‐200a‐3p, and miR‐21‐5p); pancreatic cancer (miR‐200b‐3p, miR‐483‐3p, and miR‐183‐5p); chronic lymphocytic leukemia (miR‐4521, miR‐7‐5p, and miR‐182‐5p); Hodgkin lymphoma (miR‐876‐5p); cervical cancer (miR‐429); head and neck squamous cell carcinoma (miR‐200b‐5p); and bladder cancer (miR‐148a‐3p) …”

Hippo Signaling in the Liver Regulates Organ Size, Cell Fate, and Carcinogenesis

“…Depending on the Hippo pathway component that is targeted, this can up- or down-regulate YAP/TAZ activity. miR-9-3p has been reported to specifically target TAZ in hepatoma cell lines 95 , an activity which will need to be validated in vivo . Several other microRNAs to be considered with respect to the liver include LATS2 targeting miR-135b 96 and miR-31 97 , and miR-375 which regulates YAP1 98 .…”

“…TAZ is an important transactivator of the Hippo pathway in liver cancer cells 95, 109 , although there has been no in-depth study to determine the specific roles for YAP and TAZ in the liver. Several genome-wide, chromatin immunoprecipitation studies of YAP and TAZ binding found these molecules to be interchangeable, binding to the same sites across the genome and presumably regulating the expression of similar genes 14, 15 .…”

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

“…For instance, miR-9 expression was recently reported to be significantly upregulated in non-small-cell lung cancer (NSCLC) tissues, which further promoted the growth of NSCLC cells and decreased the growth inhibitory effect of erlo-tinib 17. In contrast, miR-9 played a suppressive role by targeting TAZ in hepatocellular carcinoma cells 18. Recently, several studies revealed that miR-9 was involved in the pathogenesis of MM.…”