Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy

Jin, Haojie; Wang, Cun; Gu, Danan; Zhang, Yurong; Fan, Shao‐Hua; Xing, Shunpeng; Wang, Hui; Ruan, Haoyu; Yang, Cheng; Lv, Yuanyuan; Feng, Hugang; Yao, Ming; Qin, Wenxin

doi:10.1016/j.bbrc.2017.09.128

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…The proliferation of hepatocytes is regulated by cell cyclerelated proteins, such as cell cyclin D, cyclin E, cyclin dependent kinase (CDK). 7 Among these, studies consistently find that cyclinD1 is a critical index for liver regeneration. 8 Cyclin D includes three subunits, cyclinD1, cylinD2, and cyclin D3.…”

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confidence: 99%

“…Liver regeneration depends on the timely restoration of cellular mass, where in hepatocyte proliferation plays a prominent role. The proliferation of hepatocytes is regulated by cell cycle‐related proteins, such as cell cyclin D, cyclin E, cyclin dependent kinase (CDK) . Among these, studies consistently find that cyclinD1 is a critical index for liver regeneration .…”

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confidence: 99%

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Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy

Liu¹,

Chen

et al. 2019

Wound Repair Regeneration

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Sirtuin 6 (Sirt6) is an NAD+‐dependent deacetylase that regulates central metabolic functions such as glucose homeostasis, fat metabolism, and cell apoptosis. However, the tissue‐specific function of Sirt6 in liver regeneration remains unknown. Here, we show that liver‐specific Sirt6 knockout (Sirt6LKO) impaired liver reconstitution after 2/3 partial hepatectomy, which was attributed to an alteration of cell cycle progression. Sirt6 LKO delayed hepatocyte transition into S phase during liver regeneration, as shown by the analysis of cell cycle‐related proteins and the immuno staining of Ki‐67 and 5‐bromo‐2‐deoxyuridine (BrdU). The delayed cell cycle in Sirt6 LKO mice was attributed to the disruption of m‐TOR and Akt activity, which is an important pro‐proliferation pathway in liver regeneration. Sirt6 LKO also reduced carbon tetrachloride (CCl4)‐induced liver damage. Our results suggest that Sirt6 LKO impaired liver regeneration via delayed cell cycle and impaired m‐TOR and Akt activity.

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confidence: 99%

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confidence: 99%

Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy

Liu¹,

Chen

et al. 2019

Wound Repair Regeneration

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“…Moreover, we demonstrated that LASS2 silenced enhances chemoresistance and V-ATPase activity in bladder cancer cells 11 , 12 . A recent report demonstrated that liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy with upregulation of cyclin A, CDK2 and p-Rb 13 . In addition, combination of LASS2 and TGF-β1 was an independent and significant risk factor for overall survival and time to recurrence in patients with hepatocellular carcinoma 14 .…”

Section: Introductionmentioning

confidence: 99%

LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells

Huang¹,

Luan²,

Chen³

et al. 2018

J. Cancer

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Mitochondria coordinated a lot of vital cellular processes of energy production and distribution. Change of mitochondrial functions has been implicated in cancer progression. The present study aims to investigate the involvement of mitochondria dynamics in LASS2 induced invasion and chemoresistance of bladder cancer cells. J82 and BIU87 cell lines were used for LASS2 plasmid transfection while siRNA knockdown was carried out in 5637 cell line. Matrigel invasion assay and Annexin V/PI staining demonstrated that LASS2 negatively regulated cancer cell invasion and chemoresistance. JC-1 staining suggested that LASS2 overexpression downregulated mitochondrial membrane potential. Mitotracker staining showed that LASS2 induced mitochondrial fusion and inhibited mitochondrial fission. In addition, LASS2 overexpression downregulated expression of mitochondrial fission protein p-Drp1 Drp1 and Fis1. While depletion of LASS2 exhibited the opposite effects. Drp1 inhibitor Mdivi abolished invasion and chemoresistance induced by LASS2 siRNA. Furthermore, we found that LASS2 overexpression could inhibit phosphorylation of ERK, which act upstream of Drp1. ERK inhibitor PD98059 suppressed Drp1 phosphorylation and abrogated the effects of LASS2 depletion. In conclusion, the present study demonstrated that LASS2 inhibits bladder cancer invasion and chemoresistance through regulation of ERK-Drp1 induced mitochondrial dynamics.

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“…Therefore, it may represent a potential biomarker for several cancers. Jin et al [ 18 ] reported decreased formation of the cyclin-dependent kinase (CDK)4/cyclin D1 complex following partial hepatectomy in liver-specific LASS2 knockout mice, indicating that it may play a role in cell cycle regulation. In addition, Su et al [ 19 ] reported that overexpression of LASS2 inhibited cell proliferation by mediating the induction of G0/G1 cell cycle arrest in 293 and 293T cells, while Fan et al [ 20 ] revealed that the overexpression of LASS2 had no effect on cell cycle progression in the breast cancer cell line MCF-7/ADR.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer

et al. 2018

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BackgroundThe aim of this study was to investigate the role of LAG1 longevity-assurance homologue 2 (LASS2) in papillary thyroid cancer (PTC).MethodsImmunohistochemistry staining was conducted to explore the expression levels of LASS2 in PTC tissues and adjacent normal thyroid tissues and nodular goiter tissues. Western blotting and RT-qPCR were performed to explore the expression levels of LASS2 in three PTC cell lines (TPC-1, K1, BCPAP). An Adv-LASS2-GFP recombinant adenovirus vector was constructed and transduced into BCPAP cells. Then CCK-8 assay, colony formation assay, cell cycle distribution, and apoptosis were performed. Western blotting was used to examine the expression of p21, cyclin D1, cyclin-dependent kinase 4, p53 and p-p53.ResultsLASS2 was downregulated in PTC tissues compared with adjacent thyroid tissues or nodular goiter tissues. In addition, the expression of LASS2 was found to be associated with TNM stage and lymph node metastasis. BCPAP cells expressed the lowest LASS2 compared to TPC-1 cells or K1 cells. Overexpression of LASS2 significantly inhibited proliferation, promoted apoptosis and caused G0/G1 cell cycle arrest in BCPAP cells. Furthermore, overexpression of LASS2 significantly increased the expression of p21, inhibited the expression of cyclin D1 and cyclin-dependent kinase 4, and increased the expression of p-p53, but did not effect the expression of p53 in BCPAP cells.ConclusionOur findings indicate that overexpression of LASS2 inhibits PTC cell proliferation, promotes apoptosis and causes G0/G1 cell cycle arrest via a p53-dependent pathway. Thus, LASS2 may serve as a novel biomarker in PTC.

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Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy

Cited by 7 publications

References 35 publications

Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy

Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy

LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells

Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer

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