CRIF1 promotes the progression of non-small-cell lung cancer by SIRT3- mediated deacetylation of PYCR1

Wang, Qi; Xie, Zhanli; Li, Chang; Xu, Chun; Ding, Cheng; Ju, Sheng; Cui, Zihan; Chen, Chen; Gu, Biao; Wei, Tengteng; Zhao, Jun

doi:10.1007/s10735-022-10075-9

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Therefore, in this study, we investigated whether CRIF1 knockdown produced antitumor effects in breast cancer cells. Previous studies have demonstrated that CRIF1 is abundantly expressed in hepatocellular carcinoma, non-small cell lung cancer, and osteosarcoma [ 24 , 25 , 26 ]. CRIF1 deletion reportedly attenuates cell proliferation and metastasis; it also inhibits tumor growth in xenograft mice.…”

Section: Discussionmentioning

confidence: 99%

CRIF1 siRNA-Encapsulated PLGA Nanoparticles Suppress Tumor Growth in MCF-7 Human Breast Cancer Cells

Piao

Lee

Kim

et al. 2023

IJMS

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Mitochondrial oxidative phosphorylation (OXPHOS) system dysfunction in cancer cells has been exploited as a target for anti-cancer therapeutic intervention. The downregulation of CR6-interacting factor 1 (CRIF1), an essential mito-ribosomal factor, can impair mitochondrial function in various cell types. In this study, we investigated whether CRIF1 deficiency induced by siRNA and siRNA nanoparticles could suppress MCF-7 breast cancer growth and tumor development, respectively. Our results showed that CRIF1 silencing decreased the assembly of mitochondrial OXPHOS complexes I and II, which induced mitochondrial dysfunction, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential depolarization, and excessive mitochondrial fission. CRIF1 inhibition reduced p53-induced glycolysis and apoptosis regulator (TIGAR) expression, as well as NADPH synthesis, leading to additional increases in ROS production. The downregulation of CRIF1 suppressed cell proliferation and inhibited cell migration through the induction of G0/G1 phase cell cycle arrest in MCF-7 breast cancer cells. Similarly, the intratumoral injection of CRIF1 siRNA-encapsulated PLGA nanoparticles inhibited tumor growth, downregulated the assembly of mitochondrial OXPHOS complexes I and II, and induced the expression of cell cycle protein markers (p53, p21, and p16) in MCF-7 xenograft mice. Thus, the inhibition of mitochondrial OXPHOS protein synthesis through CRIF1 deletion destroyed mitochondrial function, leading to elevated ROS levels and inducing antitumor effects in MCF-7 cells.

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Section: Discussionmentioning

confidence: 99%

CRIF1 siRNA-Encapsulated PLGA Nanoparticles Suppress Tumor Growth in MCF-7 Human Breast Cancer Cells

Piao

Lee

Kim

et al. 2023

IJMS

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NMNAT2: An important metabolic enzyme affecting the disease progression

Li¹,

Gao²,

Hu³

et al. 2023

Biomedicine & Pharmacotherapy

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Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling

Tamang

Kumar

Patel

et al. 2023

Cells

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Background: Despite significant progress in clinical management, colorectal cancer (CRC) remains the third most common cause of cancer-related deaths. A positive association between PYCR2 (pyrroline-5-carboxylate reductase-2), a terminal enzyme of proline metabolism, and CRC aggressiveness was recently reported. However, how PYCR2 promotes colon carcinogenesis remains ill understood. Methods: A comprehensive analysis was performed using publicly available cancer databases and CRC patient cohorts. Proteomics and biochemical evaluations were performed along with genetic manipulations and in vivo tumor growth assays to gain a mechanistic understanding. Results: PYCR2 expression was significantly upregulated in CRC and associated with poor patient survival, specifically among PYCR isoforms (PYCR1, 2, and 3). The genetic inhibition of PYCR2 inhibited the tumorigenic abilities of CRC cells and in vivo tumor growth. Coinciding with these observations was a significant decrease in cellular proline content. PYCR2 overexpression promoted the tumorigenic abilities of CRC cells. Proteomics (LC-MS/MS) analysis further demonstrated that PYCR2 loss of expression in CRC cells inhibits survival and cell cycle pathways. A subsequent biochemical analysis supported the causal role of PYCR2 in regulating CRC cell survival and the cell cycle, potentially by regulating the expression of MASTL, a cell-cycle-regulating protein upregulated in CRC. Further studies revealed that PYCR2 regulates Wnt/β-catenin-signaling in manners dependent on the expression of MASTL and the cancer stem cell niche. Conclusions: PYCR2 promotes MASTL/Wnt/β-catenin signaling that, in turn, promotes cancer stem cell populations and, thus, colon carcinogenesis. Taken together, our data highlight the significance of PYCR2 as a novel therapeutic target for effectively treating aggressive colon cancer.

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CRIF1 promotes the progression of non-small-cell lung cancer by SIRT3- mediated deacetylation of PYCR1

Cited by 3 publications

References 37 publications

CRIF1 siRNA-Encapsulated PLGA Nanoparticles Suppress Tumor Growth in MCF-7 Human Breast Cancer Cells

CRIF1 siRNA-Encapsulated PLGA Nanoparticles Suppress Tumor Growth in MCF-7 Human Breast Cancer Cells

NMNAT2: An important metabolic enzyme affecting the disease progression

Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling

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