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GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma.

Yao J, Liang LH, Zhang Y, Ding J, Tian Q, Li JJ, He XH - Cancer Biol Med (2012)

Bottom Line: The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels.GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells.Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China ; State Key Laboratory for Diagnosis and Treatment for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

ABSTRACT

Objective: To explore the role and regulation of guanine nucleotide-binding protein G(i), α-1 subunit (GNAI1) in hepatocellular carcinoma (HCC).

Methods: Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAI1 was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays.

Results: The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro.

Conclusions: GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.

No MeSH data available.


Related in: MedlinePlus

MiRNA-320 can remarkably facilitate HCC cell migration and invasion. A: Transwell migration assays of SMMC-7721 cells transfected with miR-320a/c/d or negative control. Representative images are shown, with the quantification of five randomly selected fields on the right. The values (presented as the means±SEM) and the statistical significance are shown; B: Transwell invasion assays of SMMC-7721 cells transfected with miR-320a/c/d or mock control. C: Transwell migration assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC; D: Transwell invasion assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC.
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f4: MiRNA-320 can remarkably facilitate HCC cell migration and invasion. A: Transwell migration assays of SMMC-7721 cells transfected with miR-320a/c/d or negative control. Representative images are shown, with the quantification of five randomly selected fields on the right. The values (presented as the means±SEM) and the statistical significance are shown; B: Transwell invasion assays of SMMC-7721 cells transfected with miR-320a/c/d or mock control. C: Transwell migration assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC; D: Transwell invasion assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC.

Mentions: To further explore the biological functions of miRNAs in HCC cells, we ectopically expressed miR-320a/c/d or miR-9* in the HCC cell line SMMC-7721. The results showed that the overexpression of miR-320a/c/d significantly enhanced the migration and invasion of the HCC cells (Figure 4A and 4B), whereas miR-9* overexpression produced no obvious effect (data not shown). By contrast, the downregulation of the endogenous miR-320a/c/d with specific inhibitors dramatically suppressed the migration and invasion of SK-Hep-1 cells (Figure 4C and 4D). Taken together, these observations indicate that miR-320a/c/d robustly facilitate the migration and invasion of HCC cells.


GNAI1 Suppresses Tumor Cell Migration and Invasion and is Post-Transcriptionally Regulated by Mir-320a/c/d in Hepatocellular Carcinoma.

Yao J, Liang LH, Zhang Y, Ding J, Tian Q, Li JJ, He XH - Cancer Biol Med (2012)

MiRNA-320 can remarkably facilitate HCC cell migration and invasion. A: Transwell migration assays of SMMC-7721 cells transfected with miR-320a/c/d or negative control. Representative images are shown, with the quantification of five randomly selected fields on the right. The values (presented as the means±SEM) and the statistical significance are shown; B: Transwell invasion assays of SMMC-7721 cells transfected with miR-320a/c/d or mock control. C: Transwell migration assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC; D: Transwell invasion assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643671&req=5

f4: MiRNA-320 can remarkably facilitate HCC cell migration and invasion. A: Transwell migration assays of SMMC-7721 cells transfected with miR-320a/c/d or negative control. Representative images are shown, with the quantification of five randomly selected fields on the right. The values (presented as the means±SEM) and the statistical significance are shown; B: Transwell invasion assays of SMMC-7721 cells transfected with miR-320a/c/d or mock control. C: Transwell migration assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC; D: Transwell invasion assays of SK-Hep-1 cells transfected with anti-miR-320a/c/d or anti-miR-NC.
Mentions: To further explore the biological functions of miRNAs in HCC cells, we ectopically expressed miR-320a/c/d or miR-9* in the HCC cell line SMMC-7721. The results showed that the overexpression of miR-320a/c/d significantly enhanced the migration and invasion of the HCC cells (Figure 4A and 4B), whereas miR-9* overexpression produced no obvious effect (data not shown). By contrast, the downregulation of the endogenous miR-320a/c/d with specific inhibitors dramatically suppressed the migration and invasion of SK-Hep-1 cells (Figure 4C and 4D). Taken together, these observations indicate that miR-320a/c/d robustly facilitate the migration and invasion of HCC cells.

Bottom Line: The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels.GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells.Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China ; State Key Laboratory for Diagnosis and Treatment for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

ABSTRACT

Objective: To explore the role and regulation of guanine nucleotide-binding protein G(i), α-1 subunit (GNAI1) in hepatocellular carcinoma (HCC).

Methods: Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAI1 was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays.

Results: The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro.

Conclusions: GNAI1 is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.

No MeSH data available.


Related in: MedlinePlus