IFITM3 upregulates c-myc expression to promote hepatocellular carcinoma proliferation via the ERK1/2 signalling pathway.

Interferon-induced transmembrane protein 3 (IFITM3) is associated with cancer development. Proto-oncogene c-myc can promote tumor proliferation. However, collections of IFITM3 and c-myc in hepatocellular carcinoma (HCC) and the potential role and mechanisms of IFITM3 in c-myc-mediated tumor proliferation remain unclear. In this study, we investigated a positive correlation between the expression of IFITM3 and c-myc in HCC. The down-regulation of IFITM3 significantly reduced c-myc expression and inhibited the proliferation of HCC in vitro and in vivo. In addition, upregulated c-myc expression restored the decrease in cell proliferation caused by the downregulation of IFITM3, while downregulation of c-myc reduced the proliferation of HCC enhanced by IFITM3. Mechanistically, IFITM3 regulates c-myc expression via the ERK1/2 signalling pathway. In conclusion, a novel path of IFITM3-ERK1/2-c-myc regulatory circuitry was identified, and its dysfunction may lead to HCC tumorigenesis.

miR­29a suppresses the growth and metastasis of hepatocellular carcinoma through IFITM3.

The interferon-induced transmembrane protein 3 (IFITM3, also called 1­8U) gene represents dysregulated expression in various tumors and is involved in tumorigenesis and progression. However, the role of IFITM3 and its underlying mechanism in hepatocellular carcinoma (HCC) are still far from elucidated. MicroRNAs (miRNAs), a class of endogenous (approximately 22 nucleotides) small noncoding RNAs, can post­transcriptionally regulate gene expression by repressing protein translation or silencing the expression of target genes that play critical roles in various cancers. miR­29a was identified as being aberrantly expressed in a significant proportion of HCC. However, the correlation between IFITM3 and miR­29a has not been reported to date. In this study, we investigated the expression of IFITM3 in HCC and its effect on the biological behavior of HCC cells as well as the association between IFITM3 and miR­29a. We determined that IFITM3 was upregulated and miR­29a downregulated in HCC tissues and that they were associated with HCC tumor size, tumor multifocal, and venous invasion. The expression of IFITM3 in HCC tissues was negatively correlated with miR­29a expression. Additionally, IFITM3 overexpression and miR­29a nonoverexpression were related to poor prognosis of HCC patients. Knockdown of IFITM3 inhibited migration, invasion, proliferation and promoted apoptosis of HCC cells, which are consistent with the effects of upregulated miR­29a. Additionally, after upregulation of IFITM3, the invasion, migration and proliferation abilities of HL­7702 cells were increased, but the apoptosis rate was decreased. Furthermore, using a Dual­Luciferase reporter gene assay, we identified IFITM3 as a new functional target gene of miR­29a. In conclusion, our findings demonstrated that the migration, invasion, proliferation and apoptosis features of HCC cells could be regulated by miR­29a via IFITM3. Thus, the present study indicated that miR­29a and IFITM3 play critical roles in the development and progression of HCC, revealing that miR­29a and IFITM3 may be novel potential therapeutic targets for patients with HCC.

IFITM3 promotes hepatocellular carcinoma invasion and metastasis by regulating MMP9 through p38/MAPK signaling.

Interferon-induced transmembrane protein 3 (IFITM3) has been shown to be overexpressed in multiple cancers. However, the role of IFITM3 in metastasis of hepatocellular carcinoma (HCC) is still poorly understood. In this study, we showed that IFITM3 was frequently overexpressed in HCC tissues compared with adjacent nontumor tissues. Overexpression of IFITM3 was significantly correlated with tumor metastasis and poor prognosis in HCC. Knockdown of IFITM3 dramatically decreased MMP9 expression and inhibited the invasion and metastasis of HCC in vitro and in vivo. Moreover, the upregulation of MMP9 rescued the decreased migration and invasion induced by the knockdown of IFITM3, whereas the knockdown of MMP9 decreased IFITM3-enhanced HCC migration and invasion. Mechanistically, we found that IFITM3 regulates MMP9 expression through the p38/MAPK pathway. Taken together, we identified a novel IFITM3-p38/MAPK-MMP9 regulatory circuitry, the dysfunction of which drives invasive and metastatic character in HCC.

Rare anatomic variation of the right hepatic artery and accessory right hepatic artery supplying hepatocellular carcinoma: A case report and literature review.

INTRODUCTION: Each hepatic artery is functionally essential for providing blood supply to the liver, and so are variant arteries. Variant arteries, including the accessory right hepatic artery (ARHA) and replaced right hepatic artery (RRHA) are commonly described in the literature. However, they usually occur independently. Here, we report an extremely rare case that involved both an ARHA and an RRHA arising from the gastroduodenal artery (GDA) and superior mesenteric artery (SMA), respectively. To date, this situation has never been reported in the literature.They were preoperatively identified during magnetic resonance imaging (MRI) examination in a 69-year-old male patient with hepatocellular carcinoma. And they were further verified by following conventional angiography for transcatheter arterial chemoembolization (TACE) for the patient. In addition, the patient's tumor was primarily supplied by these 2 variant arteries. After the successful TACE procedure, the patient had a well postoperative recovery. CONCLUSIONS: By analyzing this case and performing a systematic review of the literature, the important clinical implications of the ARHA and RRHA will be investigated and discussed. Main lessons learned from this case thorough understanding of the normal anatomy of the hepatic artery and its anatomic variation is crucial for surgeons and interventional radiologists; preoperative computed tomography, MRI, and intraoperative angiography play an important role in detecting the variant hepatic artery; identifying these anomalous hepatic arteries before operation can effectively avoid unintentional injury during surgery, such as massive hemorrhage or hepatic infarction.