Limits...
MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin.

Zhang X, Cheng SL, Bian K, Wang L, Zhang X, Yan B, Jia LT, Zhao J, Gammoh N, Yang AG, Zhang R - Oncotarget (2015)

Bottom Line: Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins.However, whether miR-26a can also influence anoikis has not been well established.Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.

ABSTRACT
Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.

Show MeSH

Related in: MedlinePlus

Down-regulation of miR-26a expression in human HCC, especially in metastatic HCC tumors(A) Relative expression levels of miR-26a (mean ± s.d. of three independent experiments) assessed by qRT-PCR in normal hepatocyte-derived cell line (L-02) and various HCC cell lines. (B) Comparison of the expression levels of miR-26a between metastasis-free and metastatic HCC. Expression levels of total miR-26a as the average expression levels of pre-miR-26a-1 and pre-miR-26a-2 from a normalized GEO dataset (GSE6857). Vertical axes represent log (base 2) relative quantification values. P value indicates statistical significance analyzed by Student's t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385851&req=5

Figure 1: Down-regulation of miR-26a expression in human HCC, especially in metastatic HCC tumors(A) Relative expression levels of miR-26a (mean ± s.d. of three independent experiments) assessed by qRT-PCR in normal hepatocyte-derived cell line (L-02) and various HCC cell lines. (B) Comparison of the expression levels of miR-26a between metastasis-free and metastatic HCC. Expression levels of total miR-26a as the average expression levels of pre-miR-26a-1 and pre-miR-26a-2 from a normalized GEO dataset (GSE6857). Vertical axes represent log (base 2) relative quantification values. P value indicates statistical significance analyzed by Student's t test.

Mentions: To investigate the role of miR-26a in human HCC, we detected the expression levels of miR-26a in a panel of human HCC cell lines and a hepatocyte-derived immortal cell line by using qRT-PCR. The results in Figure 1A show remarkably lower levels of miR-26a in HCC cells compared to an immortalized liver cell line, in agreement with a tumor suppressor role of miR-26a in HCC. To further confirm whether miR-26a is associated with metastasis of HCC, a normalized Gene Expression Omnibus (GEO) dataset (GSE6857) was analyzed. The data show significant downregulation of miR-26a in venous metastatic cancer tissues compared to metastasis-free cancer tissues (Figure 1B). These observations are in agreement with previous findings that miR-26a expression is down-regulated in parallel with hepatocellular cancerization and metastasis [23-26].


MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin.

Zhang X, Cheng SL, Bian K, Wang L, Zhang X, Yan B, Jia LT, Zhao J, Gammoh N, Yang AG, Zhang R - Oncotarget (2015)

Down-regulation of miR-26a expression in human HCC, especially in metastatic HCC tumors(A) Relative expression levels of miR-26a (mean ± s.d. of three independent experiments) assessed by qRT-PCR in normal hepatocyte-derived cell line (L-02) and various HCC cell lines. (B) Comparison of the expression levels of miR-26a between metastasis-free and metastatic HCC. Expression levels of total miR-26a as the average expression levels of pre-miR-26a-1 and pre-miR-26a-2 from a normalized GEO dataset (GSE6857). Vertical axes represent log (base 2) relative quantification values. P value indicates statistical significance analyzed by Student's t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385851&req=5

Figure 1: Down-regulation of miR-26a expression in human HCC, especially in metastatic HCC tumors(A) Relative expression levels of miR-26a (mean ± s.d. of three independent experiments) assessed by qRT-PCR in normal hepatocyte-derived cell line (L-02) and various HCC cell lines. (B) Comparison of the expression levels of miR-26a between metastasis-free and metastatic HCC. Expression levels of total miR-26a as the average expression levels of pre-miR-26a-1 and pre-miR-26a-2 from a normalized GEO dataset (GSE6857). Vertical axes represent log (base 2) relative quantification values. P value indicates statistical significance analyzed by Student's t test.
Mentions: To investigate the role of miR-26a in human HCC, we detected the expression levels of miR-26a in a panel of human HCC cell lines and a hepatocyte-derived immortal cell line by using qRT-PCR. The results in Figure 1A show remarkably lower levels of miR-26a in HCC cells compared to an immortalized liver cell line, in agreement with a tumor suppressor role of miR-26a in HCC. To further confirm whether miR-26a is associated with metastasis of HCC, a normalized Gene Expression Omnibus (GEO) dataset (GSE6857) was analyzed. The data show significant downregulation of miR-26a in venous metastatic cancer tissues compared to metastasis-free cancer tissues (Figure 1B). These observations are in agreement with previous findings that miR-26a expression is down-regulated in parallel with hepatocellular cancerization and metastasis [23-26].

Bottom Line: Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins.However, whether miR-26a can also influence anoikis has not been well established.Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.

ABSTRACT
Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.

Show MeSH
Related in: MedlinePlus