Overexpression of RAS-Association Domain Family 6 (RASSF6) Inhibits Proliferation and Tumorigenesis in Hepatocellular Carcinoma Cells

Zhu, Nan; Si, Mahui; Jing, Yingying; Fu, Yong; Zhao, Xijun; Lin, Zhipeng; Yang, Guang-Shun

doi:10.3727/096504016x14796039599926

Cited by 8 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple members of the RASSF exhibit anticancer effects (38). RASSF6 is a novel tumor suppressor that serves an important role in the pathogenesis of various types of cancer (39,40). For instance, miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signaling activation (41).…”

Section: Discussionmentioning

confidence: 99%

lncRNA TUSC7 inhibits osteosarcoma progression through the miR‑181a/RASSF6 axis

et al. 2020

View full text Add to dashboard Cite

Osteosarcoma (OS) is one of the most aggressive malignancies, accompanied by an elevated incidence and a decreased rate of healing. Recently, several long non-coding RNAs (lncRNAs) have been reported to be involved in OS progression. Although tumor suppressor candidate 7 (TUSC7) was reported as a novel lncRNA, little is known about its biological functions in OS. The present study was designed to explore whether TUSC7 was involved in the pathological development of OS using various methods, including hematoxylin and eosin staining, Cell Counting Kit-8 assay, colony formation assay and Transwell assay. The present study revealed that TUSC7 expression was downregulated in OS tissues and cell lines compared with in normal tissues and cell lines. Functionally, the current results revealed that overexpression of TUSC7 inhibited OS cell proliferation, migration and invasion, while promoting apoptosis in vitro and in vivo . Next, the subcellular distribution of TUSC7 was examined by nuclear/cytoplasmic RNA fractionation and reverse transcription-quantitative PCR. Mechanistic studies revealed that TUSC7 exerted its role by sponging microRNA (miR)-181a in OS cell lines. Ras association domain family member 6 (RASSF6) was confirmed as a target gene of miR-181a, and the expression levels of RASSF6 were negatively regulated by miR-181a. Additionally, the results of rescue experiments suggested that overexpression of miR-181a neutralized the inhibitory effects of TUSC7 overexpression on OS cells. Overall, the present study demonstrated that the tumor suppressor role of TUSC7 in OS progression was mediated through the miR-181a/RASSF6 axis, which may represent a new therapeutic target for OS.

show abstract

Section: Discussionmentioning

confidence: 99%

lncRNA TUSC7 inhibits osteosarcoma progression through the miR‑181a/RASSF6 axis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Further gene expression profiling of these livers (when compared with the PML −/− HCV tg livers that did not develop tumors) provided numerous genes associated with increased cell proliferation. RASSF6 has been shown to be expressed in low amounts in HCC, and its overexpression correlates with decreased cell proliferation and invasion in vitro, as well as attenuated tumor growth in a rodent model . The inhibitory effects are described to be established through suppression of FAK phosphorylation, which in turn leads to decreased MMP2/9 expression .…”

Section: Discussionmentioning

confidence: 99%

“…RASSF6 has been shown to be expressed in low amounts in HCC, and its overexpression correlates with decreased cell proliferation and invasion in vitro, as well as attenuated tumor growth in a rodent model. 20 The inhibitory effects are described to be established through suppression of FAK phosphorylation, which in turn leads to decreased MMP2/9 expression. 20 Our analysis confirms this finding, since we established the downregulation of RASSF6 in liver tissue extracted from liver tumors.…”

Section: Discussionmentioning

confidence: 99%

“…20 The inhibitory effects are described to be established through suppression of FAK phosphorylation, which in turn leads to decreased MMP2/9 expression. 20 Our analysis confirms this finding, since we established the downregulation of RASSF6 in liver tissue extracted from liver tumors. Interestingly, not only the tumorous tissue but also the tumor-surrounding tissue of PML −/− HCV tg livers, and PML −/− HCV tg livers without tumor development showed a stepwise decrease in RASSF6 expression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Promyelocytic leukemia protein deficiency leads to spontaneous formation of liver tumors in hepatitis C virus transgenic mice

et al. 2019

View full text Add to dashboard Cite

Persistent infection with hepatitis C virus (HCV) is a known risk factor for the development of hepatocellular carcinoma (HCC). The lack of the tumor suppressor promyelocytic leukemia protein (PML) in combination with HCV fosters hepatocarcinogenesis via induction of HCC using diethylnitrosamine (DEN) in a rodent model. However, the spontaneous development of malignant lesions in PML‐deficient mice with an HCV‐transgene (HCV tg ) has not been investigated thus far. We crossed PML‐deficient mice with HCV transgene expressing mice and observed the animals for a period of 12 months. Livers were examined macroscopically and histologically. Gene expression analysis was performed on these samples, and compared with expression of selected genes in human samples of patients undergoing liver transplantation for HCC. In vitro studies were performed in order to analyze the selected pathways. Genetic depletion of PML in combination with HCV tg coincided with an increased hepatocyte proliferation, resulting in development of HCCs in 40% of the PML‐deficient livers. No tumor development was observed in mice with either the PML‐knockout (PML −/− ) or HCV tg alone. Gene expression profiling uncovered pathways involved in cell proliferation, such as NLRP12 and RASFF6. These findings were verified in samples from human livers of patients undergoing liver transplantation for HCC. Further in vitro studies confirmed that lack of PML, NLRP12, and RASFF6 leads to increased cell proliferation. The lack of PML in combination with HCV is associated with increased cell proliferation, fostering tumor development in the liver. Our data demonstrate that PML acts as an important tumor suppressor in HCV‐dependent liver pathology.

show abstract

“…Levels of MMP2 and MMP9 were found to be reduced in RASSF6-overexpressing-HepG2 cells. Shrinkage of the tumor xenografts was noticed in mice inoculated with RASSF6-overexpressing-HepG2 cells [ 31 ].…”

Section: Rassf6mentioning

confidence: 99%