RUNX3 inhibits growth of HCC cells and HCC xenografts in mice in combination with adriamycin

Li, Xiaohua; Zhang, Ying; Zhang, Yafei; Qiao, Tiankui; Wu, Kaijie; Ding, Jie; Liu, Jie; Fan, Daiming

doi:10.4161/cbt.7.5.5664

Cited by 9 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we evaluated the relationship between RUNX3 expression and chemosensitivity in HCC. RUNX3 was found to act as a tumor suppressor in HCC, consistent with previous studies showing that RUNX3 is frequently lost in HCC ( 23 , 27 – 29 ) and that loss of RUNX3 contributes to the malignant transformation of HCC ( 23 – 25 ).…”

Section: Discussionsupporting

confidence: 90%

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

show abstract

Section: Discussionsupporting

confidence: 90%

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Furthermore, RUNX3 is a marker of chemosensitivity. RUNX3 overexpression sensitized gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1, and MRP-1 [122], while in HCC, RUNX3 in combination with adriamycin enhanced caspase-8 and inhibited Bcl-2 and suppressed tumor growth in vivo and in vitro [123]. Similar observations were also noted with CRCs [114].…”

Section: Therapeutic Implicationsmentioning

confidence: 57%

Molecular pathology of RUNX3 in human carcinogenesis

Subramaniam

Chan

Yeoh

et al. 2009

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

109

View full text Add to dashboard Cite

A major goal of molecular biology is to elucidate the mechanisms underlying cancer development and progression in order to achieve early detection, better diagnosis and staging and novel preventive and therapeutic strategies. We feel that an understanding of Runt-related transcription factor 3 (RUNX3)-regulated biological pathways will directly impact our knowledge of these areas of human carcinogenesis. The RUNX3 transcription factor is a downstream effector of the transforming growth factor-beta (TGF-beta) signaling pathway, and has a critical role in the regulation of cell proliferation and cell death by apoptosis, and in angiogenesis, cell adhesion and invasion. We previously identified RUNX3 as a major gastric tumor suppressor by establishing a causal relationship between loss of function and gastric carcinogenesis. More recently, we showed that RUNX3 functions as a bona fide initiator of colonic carcinogenesis by linking the Wnt oncogenic and TGF-beta tumor suppressive pathways. Apart from gastric and colorectal cancers, a multitude of epithelial cancers exhibit inactivation of RUNX3, thereby making it a putative tumor suppressor in human neoplasia. This review highlights our current understanding of the molecular mechanisms of RUNX3 inactivation in the context of cancer development and progression.

show abstract

“…Therefore, it is not surprising that RUNX3 gene expression decreases in HCC and other human malignancies, including those of the colon, lung, pancreas and bile duct 32–35. Several authors have reported that RUNX3 gene and protein expression is decreased in HCC and that loss of RUNX3 expression prevented apoptosis in HCC cells 36–39. We also reported that ectopic RUNX3 expression deactivated Notch signaling by decreasing jagged‐1 (JAG1) expression in HCC 40.…”

mentioning

confidence: 79%

“…RUNX3 expression is generally reduced in human HCC tissues 36, 38. However, the role of decreased RUNX3 expression in the development and progression of HCC has not yet been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Runt‐related transcription factor 3 reverses epithelial–mesenchymal transition in hepatocellular carcinoma

Tanaka

Shiraha

Nakanishi

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelial-mesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low-and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased Ecadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low-and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

show abstract

RUNX3 inhibits growth of HCC cells and HCC xenografts in mice in combination with adriamycin

Cited by 9 publications

References 21 publications

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

Molecular pathology of RUNX3 in human carcinogenesis

Runt‐related transcription factor 3 reverses epithelial–mesenchymal transition in hepatocellular carcinoma

Contact Info

Product

Resources

About