Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes.

INTRODUCTION: This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). MATERIALS: A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1yr=2.62, 95%CI: 1.76-3.90; OR3yr=3.14, 95%CI: 2.33-4.24; OR5yr=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR1yr=2.52, 95%CI: 1.84-3.44; OR3yr=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR5yr=2.26, 95%CI: 0.94-5.45, P=0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2>50%). CONCLUSIONS: Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.

miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting Sirt1.

BACKGROUND: miR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers. However, the role of miR-22 in regulating the radioresistance of breast cancer cells, as well as its underlying mechanism is still not well understood. METHODS: The expressions of miR-22 and sirt1 at mRNA and protein levels were examined by qRT-PCR and Western Blot. The effects of miR-22 overexpression and sirt1 knockdown on cell viability, apoptosis, radiosensitivity, γ-H2AX foci formation were evaluated by CCK-8 assay, flow cytometry, colony formation assay, and γ-H2AX foci formation assay, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm the interaction between miR-22 and sirt1. RESULTS: miR-22 was downregulated and sirt1 was upregulated at both mRNA and protein levels in breast cancer cells. miR-22 overexpression or sirt1 knockdown significantly suppressed viability, induced apoptosis, reduced survival fraction, and increased the number of γ-H2AX foci in breast cancer cells. Sirt1 was identified as a target of miR-22 and miR-22 negatively regulated sirt1 expression. Ectopic expression of sirt1 dramatically reversed the inhibitory effect of miR-22 on cell viability and promotive effect on apoptotic rates and radiosensitivity in breast cancer cells. CONCLUSIONS: miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting sirt1, providing a promising therapeutic target for breast cancer.

miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting Sirt1

BACKGROUND: miR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers. However, the role of miR-22 in regulating the radioresistance of breast cancer cells, as well as its underlying mechanism is still not well understood. METHODS: The expressions of miR-22 and sirt1 at mRNA and protein levels were examined by qRT-PCR and Western Blot. The effects of miR-22 overexpression and sirt1 knockdown on cell viability, apoptosis, radiosensitivity, γ-H2AX foci formation were evaluated by CCK-8 assay, flow cytometry, colony formation assay, and γ-H2AX foci formation assay, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm the interaction between miR-22 and sirt1. RESULTS: miR-22 was downregulated and sirt1 was upregulated at both mRNA and protein levels in breast cancer cells. miR-22 overexpression or sirt1 knockdown significantly suppressed viability, induced apoptosis, reduced survival fraction, and increased the number of γ-H2AX foci in breast cancer cells. Sirt1 was identified as a target of miR-22 and miR-22 negatively regulated sirt1 expression. Ectopic expression of sirt1 dramatically reversed the inhibitory effect of miR-22 on cell viability and promotive effect on apoptotic rates and radiosensitivity in breast cancer cells. CONCLUSIONS: miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting sirt1, providing a promising therapeutic target for breast cancer.