Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression

Xia, Limin; Huang, Wenjie; Tian, Dean; Zhang, Lin; Qi, Xingshun; Chen, Zhangqian; Shang, Xin; Nie, Yongzhan; Wu, Kaichun

doi:10.1002/hep.26735

Cited by 141 publications

(124 citation statements)

References 33 publications

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“…It has previously been revealed that FOXQ1 is overexpressed in various types of human cancer, including colorectal (44), breast (45) and lung cancer (45) and HCC (46,47). Notably, high FOXQ1 expression levels were independent prognostic factors of HCC (46).…”

Section: Discussionmentioning

confidence: 96%

MicroRNA‑1271 inhibits cellular proliferation of hepatocellular carcinoma

et al. 2017

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide, particularly in China. MicroRNAs (miRs) serve important roles in the pathogenesis of HCC. The present study investigated the function of miR-1271 in HCC. The miR-1271 levels were analyzed by quantitative reverse transcription polymerase chain reaction. Cells growth was examined by MTT assay. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-1271. The protein level was assayed by western blotting. miR-1271 demonstrated a lower expression level in HCC tissues. Upregulation of miR-1271 suppressed the growth of HepG-2 and Huh-7 cells and induced apoptosis of cells. Forkhead box Q1 (FOXQ1) was targeted by miR-1271. In conclusion, miR-1271 is a novel tumor suppressor that inhibits HCC proliferation and induces cellular apoptosis by targeting FOXQ1 in HCC. The results of the present study may provide a novel therapeutic target of HCC. IntroductionHepatocellular carcinoma (HCC) accounts for ~80% of all liver cancer cases, and is one of the most common causes of cancer-associated mortality worldwide (1,2). The prevalence rate of HCC in China is particularly high, but continues to increase in numerous western countries (1,3). Despite HCC being was one of the first cancers to be linked epidemiologically to a definite risk factor, the underlying mechanisms of HCC pathogenesis remain unclear (4). The risk factors for HCC vary by location. In China, Hepatitis B or Hepatitis C virus infections are the main risk factors (5). The survival rate of patients with HCC has been extended due to progress in liver transplantation and other treatments; however, the insensitivity of chemotherapeutic drugs, cancer recurrence and metastasis continue to contribute to a poor prognosis (6). Thus, the identification of therapeutic targets and translation of molecular studies of HCC into clinical practice is urgently required.MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are ~22 nucleotides in length (7-9). A number of miRNAs have been revealed to be involved in the pathogenesis of HCC (10-26). The roles of miR-1271 in numerous types of cancers have previously been investigated. For example, in gastric cancer, miR-1271 inhibited cell proliferation, invasion and epithelial-mesenchymal transition (EMT) by targeting forkhead box Q1 (FOXQ1) (27). Additionally, in oral squamous cell carcinoma, miR-1271 inhibited cell growth and metastasis by targeting anaplastic lymphoma receptor tyrosine kinase (28). In HCC, a previous study demonstrated that miR-96, miR-129-1-3p, miR-1291, miR-1303 and miR-1271 differentially regulated Glypican-3 (GPC3) expression levels in HCC cells and that the upregulation of GPC3 was associated with a concomitant downregulation of its repressor miR-1271 (29). However, the roles served by miR-1271 in HCC remain unclear.The present study analyzed the expression level of miR-1271 in HCC tissues and determined the in vitro function of miR-1271. The aim of the ...

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Section: Discussionmentioning

confidence: 96%

MicroRNA‑1271 inhibits cellular proliferation of hepatocellular carcinoma

et al. 2017

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“…FOX proteins are a family of transcription factors, which regulate the expression of target genes involved in cellular differentiation, growth and proliferation (47). The family consists of the FOXA1, FOXA2, and FOXA3 proteins.…”

Section: Ar and Hbvmentioning

confidence: 99%

Androgen receptor in hepatocarcinogenesis: Recent developments and perspectives

et al. 2015

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Abstract. Previous studies have indicated that males are at a higher risk of developing hepatocellular carcinoma (HCC) compared with females. Identifying the factors that cause this gender-specific difference in the incidence of HCC has long been considered important for revealing the molecular mechanisms involved in hepatocarcinogenesis. Given the unprecedented tools that are now available for molecular research, genetic studies have established that the androgen receptor (AR) may be partly responsible for gender disparity in HCC. AR has a dual role, promoting HCC initiation and development, as well as suppressing HCC metastasis. The present review provides an overview of the involvement of AR signaling in HCC. The review highlighted important studies, examples of the direct AR transcriptional target genes involved in HCC and novel theories concerning the conventional concept, suggesting that targeting the AR, rather than the androgen, may provide an improved therapeutic approach for the treatment of HCC.

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“…FOXQ1 induced metastasis through regulation of VersicanV1, which promoted tumorassociated-macrophages attraction. Also, similarly to colorectal cancer expression of FOXQ1 was regulated by the Wnt pathway in hepatocarcinoma (Xia et al, 2014).…”

Section: Hepatocarcinomamentioning

confidence: 91%

“…Cytogenetics FOXQ1 correlated with overall worse survival and higher recurrence Xia et al, 2014). Oncogenesis In hepatocarcinoma FOXQ1 directly activated the EMT transcription factor ZEB2.…”

Section: Hepatocarcinomamentioning

confidence: 96%