LHPP suppresses gastric cancer progression via the PI3K/AKT/mTOR signaling pathway

Wang, Danfang; Li, Jianhui; Li, Wenhan

doi:10.7150/jca.78098

Cited by 10 publications

(5 citation statements)

References 31 publications

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“…Subsequent studies have confirmed that LHPP expression level is negatively correlated with cell cycle progression and metastasis in human HCC tissues and forced overexpression of LHPP inhibited the growth and metastasis of various human hepatoma cells [ 15 ]. A similar tumor suppressor role has been reported in other types of cancer such as cervical cancer [ 16 ], gastric cancer [ 17 , 18 ], thyroid cancer [ 19 ], bladder cancer [ 20 ], colorectal cancer [ 21 ] and glioblastoma [ 22 ]. Therefore, restoring the function of LHPP may serve as a potential therapeutic target for HCC and other types of tumors.…”

Section: Introductionsupporting

confidence: 67%

Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth

Bi,

Kang,

Qian

et al. 2024

PLoS ONE

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism. Here we designed and validated saRNAs that could activate LHPP expression at both the mRNA and protein levels in HCC cells. Activation of LHPP by its saRNAs led to the suppression of HCC proliferation, migration and the inhibition of Akt phosphorylation. When combined with targeted anticancer drugs (e.g., regorafenib), LHPP saRNA exhibited synergistic effect in inhibiting in vitro HCC proliferation and in vivo antitumor growth in a xenograft HCC model. Findings from this study provides further evidence for a tumor suppressor role of LHPP and potential therapeutic value of restoring the expression of LHPP by saRNA for the treatment of HCC.

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Section: Introductionsupporting

confidence: 67%

Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth

Bi,

Kang,

Qian

et al. 2024

PLoS ONE

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show abstract

“…LHPP is a histidine phosphatase, and recently LHPP has been identified to be a tumour suppressor in HCC and other cancers 31,32 , which can inhibit tumour cell proliferation and metastasis, and induce apoptosis in numerous tumor cells by affecting different target genes 33 . Mechanically, tumor suppression activity of LHPP may be mediated through inhibiting EGFR 34 , modulating AKT/mTOR 35,36 and TGF-β/smad signaling pathway 18 etc. Recent study also proved that loss of LHPP is associated with intestinal inflammation in colitis mice model and inflammatory bowel disease patients 21 , showing that vital roles of LHPP in maintenance of normal body functions.…”

Section: Discussionmentioning

confidence: 99%

Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer

Zhao,

Liu,

Zhan

et al. 2024

Sci Rep

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LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

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“…Additionally, drugs targeting the PI3K/AKT/mTOR pathway in combination with chemotherapeutic drugs are considered promising treatment approaches [ 47 ]. Several genes have been reported to influence cell cycle, apoptosis, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in cancer [ 48 – 50 ]. Moreover, Zhang et al [ 51 ] reported that proliferation of human mesangial cells and PI3K/Akt/mTOR activation were dependent on TfR, by showing that PI3K/Akt/mTOR was inhibited by the human TfR polyclonal antibody.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway

Feng,

Arima,

Midorikawa

et al. 2023

Cancer Cell Int

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Background The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. Methods The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. Results TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. Conclusions These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

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LHPP suppresses gastric cancer progression via the PI3K/AKT/mTOR signaling pathway

Cited by 10 publications

References 31 publications

Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth

Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth

Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer

Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway

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