Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53

Jung, Ji Hoon; Lee, Duckgue; Ko, Hyun Min; Jang, Hyeung-Jin

doi:10.3390/biom11101492

Cited by 14 publications

(24 citation statements)

References 19 publications

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“…In addition, c-Myc is involved in cell proliferation, cell cycle, metabolism, and survival in cancer cells [ 29 ]. Previously, we showed that the inhibition of CCR4-NOT transcription complex subunit 2 (CNOT2) induces apoptosis through MID1IP1 by activating p53 [ 17 ]. Furthermore, previous studies have shown that MID1IP1 regulates cancer cell growth through c-Myc regulation [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies [ 17 ] showed that knockdown of CNOT2 induces apoptosis with MID1IP1 in colon cancer cells via p53 activation. Furthermore, MID1IP1 regulates liver cancer growth through c-Myc mediated by CNOT2.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study showed that CNOT2 is related to MID1IP1 in regulating the expression of c-Myc and inducing apoptosis in cancer cells [ 8 ]. Additionally, knockdown of CNOT2 induces p53 expression and apoptosis via MID1IP1 [ 17 ]. From previous results, it can be considered that TA3 causes apoptosis through these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…The cytotoxicity assay was performed as described in a previous study [ 17 ]. HCT116 p53−/− cells were distributed in 96-well plates (1 × 10 4 cells/well), and, the next day, they were treated with TA3 at a concentration range of 0–25 µM for 24 h.…”

Section: Methodsmentioning

confidence: 99%

“…CNOT2 is a subunit of the CCR4-NOT complex that controls mRNA metabolism and the stability of eukaryotic cells and has been reported to play a role in autophagy, apoptosis, proliferation, and angiogenesis in various cancer cells, including those of the colon, lung, and breast [ 14 , 15 , 16 , 17 ]. MID1IP1 is a gene that regulates acetyl-CoA carboxylase in the liver and promotes adipogenesis by activating the liver-X receptor; its role as an oncogene has recently been revealed [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The Antitumor Effect of Timosaponin A3 through c-Myc Inhibition in Colorectal Cancer Cells and Combined Treatment Effect with 5-FU or Doxorubicin

Jee

Park

et al. 2022

IJMS

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Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhena asphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer’s disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Antitumor Effect of Timosaponin A3 through c-Myc Inhibition in Colorectal Cancer Cells and Combined Treatment Effect with 5-FU or Doxorubicin

Jee

Park

et al. 2022

IJMS

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Momordicae Semen inhibits migration and induces apoptotic cell death by regulating c-Myc and CNOT2 in human pancreatic cancer cells

Jee,

Ko,

Park

et al. 2023

Sci Rep

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Pancreatic cancer(PC) is less common than other cancers; however, it has a poor prognosis. Therefore, studying novel target signaling and anticancer agents is necessary. Momordicae Semen (MS), the seed of Momordica sochinensis Spreng, mainly found in South-East Asia, including China and Bangladesh, is used to treat various diseases because of its anticancer, antioxidant, anti-inflammatory, and antibacterial properties. However, the effect of the MS extract on pancreatic cancer cells remains unknown. In this study investigated whether the MS extract exerted an anti-cancer effect by regulating c-Myc through CNOT2. Cytotoxicity and proliferation were investigated using MTT and colony formation assays. The levels of apoptotic, oncogenic, and migration-associated factors were confirmed using immunoblotting and immunofluorescence. Wound closure was analyzed using a wound healing assay. The chemical composition of the MS methanol extracts was analyzed using liquid chromatography–mass spectrometry. We confirmed that the MS extract regulated apoptotic factors and attenuated the stability of c-Myc and its sensitivity to fetal bovine serum. Furthermore, the MS extract increased apoptosis by regulating c-Myc and CNOT2 expression and enhanced the sensitivity of 5-FU in pancreatic cancer. This study showed that the MS extract is a promising new drug for PC.

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Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC

et al. 2023

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Background and Aims: Understanding the mechanisms of HCC progression and metastasis is crucial to improve early diagnosis and treatment. This study aimed to identify key molecular targets involved in HCC metastasis. Approach and Results: Using whole-transcriptome sequencing of patients’ HCCs, we identified and validated midline 1 interacting protein 1 (MID1IP1) as one of the most significantly upregulated genes in metastatic HCCs, suggesting its potential role in HCC metastasis. Clinicopathological correlation demonstrated that MID1IP1 upregulation significantly correlated with more aggressive tumor phenotypes and poorer patient overall survival rates. Functionally, overexpression of MID1IP1 significantly promoted the migratory and invasive abilities and enhanced the sphere-forming ability and expression of cancer stemness-related genes of HCC cells, whereas its stable knockdown abrogated these effects. Perturbation of MID1IP1 led to significant tumor shrinkage and reduced pulmonary metastases in an orthotopic liver injection mouse model and reduced pulmonary metastases in a tail-vein injection model in vivo. Mechanistically, SP1 transcriptional factor was found to be an upstream driver of MID1IP1 transcription. Furthermore, transcriptomic sequencing on MID1IP1-overexpressing HCC cells identified FOS-like 1 (FRA1) as a critical downstream mediator of MID1IP1. MID1IP1 upregulated FRA1 to subsequently promote its transcriptional activity and extracellular matrix degradation activity of matrix metalloproteinase MMP9, while knockdown of FRA1 effectively abolished the MID1IP1-induced migratory and invasive abilities. Conclusions: Our study identified MID1IP1 as a regulator in promoting FRA1-mediated-MMP9 signaling and demonstrated its role in HCC metastasis. Targeting MID1IP1-mediated FRA1 pathway may serve as a potential therapeutic strategy against HCC progression.

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Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53

Cited by 14 publications

References 19 publications

The Antitumor Effect of Timosaponin A3 through c-Myc Inhibition in Colorectal Cancer Cells and Combined Treatment Effect with 5-FU or Doxorubicin

The Antitumor Effect of Timosaponin A3 through c-Myc Inhibition in Colorectal Cancer Cells and Combined Treatment Effect with 5-FU or Doxorubicin

Momordicae Semen inhibits migration and induces apoptotic cell death by regulating c-Myc and CNOT2 in human pancreatic cancer cells

Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC

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