Metformin inhibits oral squamous cell carcinoma progression through regulating RNA alternative splicing

Ji, Minmin; Lv, Yuesheng; Chen, Chaoqun; Xing, Dingya; Zhou, Chao; Zhao, Jie; Qi, Yangfan; Zhang, Jinrui; Wang, Yan; Ma, Xiang; Xu, Wei; Zhang, Wenjing; Li, Xiaojie

doi:10.1016/j.lfs.2022.121274

Cited by 4 publications

(6 citation statements)

References 49 publications

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“…Aberrant splicing events can result in cancer ( 97 ). Metformin is reported to be involved in 1521 alternative splicing events involved in processes including: centrosome function, DNA damage, ATPase activity, RIG-I-like receptor signaling pathway and Wnt signaling ( 98 ). Among them, exon 3 skipping of nucleotide binding protein 2 (NUBP2), an ATP-binding protein, was increased following metformin treatment ( 98 ).…”

Section: Discussionmentioning

confidence: 99%

“…Metformin is reported to be involved in 1521 alternative splicing events involved in processes including: centrosome function, DNA damage, ATPase activity, RIG-I-like receptor signaling pathway and Wnt signaling ( 98 ). Among them, exon 3 skipping of nucleotide binding protein 2 (NUBP2), an ATP-binding protein, was increased following metformin treatment ( 98 ). Metformin induces a splicing switch to the canonical long isoform, which in turn reduces intracellular ATP to inhibit cancer cell proliferation and reduce colony formation ( 98 ).…”

Section: Discussionmentioning

confidence: 99%

“…Among them, exon 3 skipping of nucleotide binding protein 2 (NUBP2), an ATP-binding protein, was increased following metformin treatment ( 98 ). Metformin induces a splicing switch to the canonical long isoform, which in turn reduces intracellular ATP to inhibit cancer cell proliferation and reduce colony formation ( 98 ).…”

Section: Discussionmentioning

confidence: 99%

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The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review

Huang,

Woods,

Dharmawardana

et al. 2024

Front. Oncol.

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This scoping review identifies the mechanistic pathways of metformin when used to treat head and neck cancer cells, in the pre-clinical setting. Understanding the underlying mechanisms will inform future experimental designs exploring metformin as a potential adjuvant for head and neck cancer. This scoping review was conducted according to the Joanna-Briggs Institute framework. A structured search identified 1288 studies, of which 52 studies fulfilled the eligibility screen. The studies are presented in themes addressing hallmarks of cancer. Most of the studies demonstrated encouraging anti-proliferative effects in vitro and reduced tumor weight and volume in animal models. However, a few studies have cautioned the use of metformin which supported cancer cell growth under certain conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review

Huang,

Woods,

Dharmawardana

et al. 2024

Front. Oncol.

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“…For example, metformin, a drug used to treat diabetes, has been shown to inhibit CSC growth and reduce tumor formation in preclinical models. 61 , 62 Combination therapy : Combining CSC-targeted therapies with conventional chemotherapy or radiation therapy may offer a more effective treatment strategy. For example, the combination of a Wnt/β-catenin pathway inhibitor and 5-fluorouracil (5-FU) has been shown to reduce tumor growth and increase survival in preclinical models.…”

Section: Potential Therapeutic Strategies Targeting Cancer Stem Cells...mentioning

confidence: 99%

“…For example, metformin, a drug used to treat diabetes, has been shown to inhibit CSC growth and reduce tumor formation in preclinical models. 61 , 62 …”

Section: Potential Therapeutic Strategies Targeting Cancer Stem Cells...mentioning

confidence: 99%

Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer

Omran,

Fouda,

Mekkawy

et al. 2024

Technol Cancer Res Treat

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Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-β, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

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Abnormal upregulation of NUBP2 contributes to cancer progression in colorectal cancer

Lan,

Wang,

Sun

et al. 2024

Mol Cell Biochem

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Colorectal cancer (CRC), a digestive tract malignancy with high mortality and morbidity, lacks effective biomarkers for clinical prognosis due to its complex molecular pathogenesis. Nucleotide binding protein 2 (NUBP2) plays a vital role in the assembly of cytosolic Fe/S protein and has been implicated in cancer progression. In this study, we found that NUBP2 was highly expressed in CRC by TCGA database analysis. Subsequently, we verified the expression of NUBP2 in CRC tumor tissues and para-carcinoma tissues using IHC staining, and further investigated its association with clinicopathological parameters. In vitro cell experiments were conducted to assess the role of NUBP2 in CRC by evaluating cell proliferation, migration, and apoptosis upon NUBP2 dysregulation. Furthermore, we established a subcutaneous CRC model to evaluate the impact of NUBP2 on tumor growth in vivo. Additionally, we performed mechanistic exploration using a Human Phospho-Kinase Array-Membrane. Our results showed higher expression of NUBP2 in CRC tissues, which positively correlated with the pathological stage, indicating its involvement in tumor malignancy. Functional studies demonstrated that NUBP2 knockdown reduced cell proliferation, increased apoptosis, and impaired migration ability. Moreover, NUBP2 knockdown inhibited tumor growth in mice. We also observed significant changes in the phosphorylation level of GSK3β upon NUBP2 knockdown or overexpression. Additionally, treatment with CHIR-99021 HCl, an inhibitor of GSK3β, reversed the malignant phenotype induced by NUBP2 overexpression. Overall, this study elucidated the functional role of NUBP2 in CRC progression both in vitro and in vivo, providing insights into the molecular mechanisms underlying CRC and potential implications for targeted therapeutic strategies.

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Metformin inhibits oral squamous cell carcinoma progression through regulating RNA alternative splicing

Cited by 4 publications

References 49 publications

The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review

The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review

Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer

Abnormal upregulation of NUBP2 contributes to cancer progression in colorectal cancer

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