Donor mi<scp>R</scp>‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a <scp>H</scp>an <scp>C</scp>hinese population

Xu, Xiao; Ling, Qi; Wang, Jianguo; Xie, Haiyang; Wei, Xuyong; Lu, Di; Hu, Qichao; Zhang, Xuanyu; Wu, Liming; Zhou, Lin

doi:10.1002/ijc.29821

Cited by 28 publications

(15 citation statements)

References 35 publications

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“…The detailed information for the Lv system will be provided on request. The mice were injected with 100 μL of virus via the tail vein according to our previous procedure . The infection efficiency was evaluated by both detection of bioluminescence using an IVIS Lumina LT Series IIIimager (Caliper Life Sciences) and crtc2 expression in the liver using real‐time polymerase chain reaction (PCR).…”

Section: Methodsmentioning

confidence: 99%

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The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

Ling

Huang

Han

et al. 2020

American Journal of Transplantation

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Tacrolimus (TAC), the mainstay of maintenance immunosuppressive agents, plays a crucial role in new‐onset diabetes after transplant (NODAT). Previous studies investigating the diabetogenic effects of TAC have focused on the β cells of islets. In this study, we found that TAC contributed to NODAT through directly affecting hepatic metabolic homeostasis. In mice, TAC‐induced hypoglycemia rather than hyperglycemia during starvation via suppressing gluconeogenetic genes, suggesting the limitation of fasting blood glucose in the diagnosis of NODAT. In addition, TAC caused hepatic insulin resistance and triglyceride accumulation through insulin receptor substrate (IRS)2/AKT and sterol regulatory element binding protein (SREBP1) signaling, respectively. Furthermore, we found a pivotal role of CREB‐regulated transcription coactivator 2 (CRTC2) in TAC‐induced metabolic disorders. The restoration of hepatic CRTC2 alleviated the metabolic disorders through its downstream molecules (eg, PCK1, IRS2, and SREBP1). Consistent with the findings from bench, low CRTC2 expression in graft hepatocytes was an independent risk factor for NODAT (odds ratio = 2.692, P = .023, n = 135). Integrating grafts’ CRTC2 score into the clinical model could significantly increase the predictive capacity (areas under the receiver operating characteristic curve: 0.71 vs 0.79, P = .048). Taken together, in addition to its impact on pancreatic cells, TAC induces “hematogenous diabetes” via CRTC2 signaling. Liver‐targeted management may be of help to prevent or heal TAC‐associated diabetes.

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Section: Methodsmentioning

confidence: 99%

“…The mice were injected with 100 μL of virus via the tail vein according to our previous procedure. 14…”

Section: Lentiviral Infection Of Mouse Livermentioning

confidence: 99%

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

Ling

Huang

Han

et al. 2020

American Journal of Transplantation

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“…The miR-196 family consists of miR-196a and miR-196b with shared regulatory capacity (3). Studies have shown that miR-196a and miR-196b exert various functions in cancer carcinogenesis and development (4)(5)(6)(7). miR-196a-2 polymorphism is associated with susceptibility to HCC and recurrence after liver transplantation (4,8).…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that miR-196a and miR-196b exert various functions in cancer carcinogenesis and development (4)(5)(6)(7). miR-196a-2 polymorphism is associated with susceptibility to HCC and recurrence after liver transplantation (4,8). A recent study found that upregulation of miR-196b is indicative of liver metastasis in patients with colorectal cancer (9).…”

Section: Introductionmentioning

confidence: 99%

microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma

Lin

Tian

et al. 2017

Oncol Rep

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Accumulating evidence indicates that microRNAs (miRNAs) play important roles in tumorigenesis and metastasis. Recent research has shown that miR‑196b is implicated in metastasis by regulating the migration and invasion of cancer cells. However, the clinical significance of miR‑196b and its role as well as the underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unknown. Here, we detected miR‑196b expression in HCC and matched non-tumor tissues with qRT‑PCR. We found that miR‑196b displayed higher expression in HCC patient tissues and cells. Clinical analysis revealed that high miR‑196 expression was correlated with venous infiltration, advanced TNM stage and poor prognosis. Functionally, we demonstrated that miR‑196b promoted the migration and invasion of HCC cells in vitro. Moreover, miR‑196b knockdown restrained pulmonary metastasis in vivo. Mechanistically, we confirmed that miR‑196b could directly bind to 3'UTR of forkhead box P2 (FOXP2) mRNA and repress its expression. miR‑196b and FOXP2 showed a negative correlation in HCC tissues. More importantly, upregulation of FOXP2 antagonized miR‑196b‑mediated migration and invasion in Hep3B cells. Furthermore, FOXP2 knockdown partially reversed the anti‑metastatic function of the miR‑196b inhibitor on HCCLM3 cells. Taken together, we demonstrated that miR‑196b may function as a prognostic biomarker and suppressed FOXP2 expression, subsequently leading to the metastasis of HCC. Our findings highlight a novel mechanism of miR‑196b in the progression of HCC and identify miR‑196b/FOXP2 axis as a promising target for HCC.

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“…It was recently reported that miR-196a polymorphism is associated with HCC cancer risk (38) and recurrence (39). Therefore, we reasoned that miR-196a might be highly expressed in HCC cells and may serve as a novel target for sensing HCC cells.…”

Section: Resultsmentioning

confidence: 99%

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

Lin

Tseng

Shen

et al. 2018

Nucleic Acids Research

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Baculovirus (BV) holds promise as a vector for anticancer gene delivery to combat the most common liver cancer–hepatocellular carcinoma (HCC). However, in vivo BV administration inevitably results in BV entry into non-HCC normal cells, leaky anticancer gene expression and possible toxicity. To improve the safety, we employed synthetic biology to engineer BV for transgene expression regulation. We first uncovered that miR-196a and miR-126 are exclusively expressed in HCC and normal cells, respectively, which allowed us to engineer a sensor based on distinct miRNA expression signature. We next assembled a synthetic switch by coupling the miRNA sensor and RNA binding protein L7Ae for translational repression, and incorporated the entire device into a single BV. The recombinant BV efficiently entered HCC and normal cells and enabled cis-acting transgene expression control, by turning OFF transgene expression in normal cells while switching ON transgene expression in HCC cells. Using pro-apoptotic hBax as the transgene, the switch-based BV selectively killed HCC cells in separate culture and mixed culture of HCC and normal cells. These data demonstrate the potential of synthetic switch-based BV to distinguish HCC and non-HCC normal cells for selective transgene expression control and killing of HCC cells.

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Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Cited by 28 publications

References 35 publications

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside

microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma

Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells

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