MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

Zhou, Xin; Li, Shaojie; Ma, Tiexiang; Zeng, Jian; Li, Huanyu; Liu, Xiang; Li, Feng; Jiang, Bin; Zhao, Ming; Liu, Zhuo; Qin, Yiyu

doi:10.3892/etm.2021.10778

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…In this study, we categorized HCC patients into three m7G clusters using consistent clustering and screened five prognostic m7G‐related genes, namely, MEX3A, G6PD, FAM83D, SPP1 and ADH. MEX3A functions as an oncogene in various cancers, including in breast and colorectal cancers 47,48 . In addition, Lu et al showed that MEX3A can promote angiogenesis in colorectal cancer through activating the glycolytic pathway, and concluded that MEX3A is a novel therapeutic target for cancer treatment 49 .…”

Section: Discussionmentioning

confidence: 99%

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Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification

Yue,

Tao,

et al. 2023

The Journal of Gene Medicine

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BackgroundThe current research investigated the heterogeneity of hepatocellular carcinoma (HCC) based on the expression of N7‐methylguanosine (m7G)‐related genes as a classification model and developed a risk model predictive of HCC prognosis, key pathological behaviors and molecular events of HCC.MethodsThe RNA sequencing data of HCC were extracted from The Cancer Genome Atlas (TCGA)‐live cancer (LIHC) database, hepatocellular carcinoman database (HCCDB) and Gene Expression Omnibus database, respectively. According to the expression level of 29 m7G‐related genes, a consensus clustering analysis was conducted. The least absolute shrinkage and selection operator (LASSO) regression analysis and COX regression algorithm were applied to create a risk prediction model based on normalized expression of five characteristic genes weighted by coefficients. Tumor microenvironment (TME) analysis was performed using the MCP‐Counter, TIMER, CIBERSORT and ESTIMATE algorithms. The Tumor Immune Dysfunction and Exclusion algorithm was applied to assess the responses to immunotherapy in different clusters and risk groups. In addition, patient sensitivity to common chemotherapeutic drugs was determined by the biochemical half‐maximal inhibitory concentration using the R package pRRophetic.ResultsThree molecular subtypes of HCC were defined based on the expression level of m7G‐associated genes, each of which had its specific survival rate, genomic variation status, TME status and immunotherapy response. In addition, drug sensitivity analysis showed that the C1 subtype was more sensitive to a number of conventional oncolytic drugs (including paclitaxel, imatinib, CGP‐082996, pyrimethamine, salubrinal and vinorelbine). The current five‐gene risk prediction model accurately predicted HCC prognosis and revealed the degree of somatic mutations, immune microenvironment status and specific biological events.ConclusionIn this study, three heterogeneous molecular subtypes of HCC were defined based on m7G‐related genes as a classification model, and a five‐gene risk prediction model was created for predicting HCC prognosis, providing a potential assessment tool for understanding the genomic variation, immune microenvironment status and key pathological mechanisms during HCC development.

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Section: Discussionmentioning

confidence: 99%

“…MEX3A functions as an oncogene in various cancers, including in breast and colorectal cancers. 47,48 In addition, Lu et al…”

Section: Specific Biological Functions Of Risk Scorementioning

confidence: 99%

Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification

Yue,

Tao,

et al. 2023

The Journal of Gene Medicine

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“…Mex3 RNA-binding family member A (MEX3A) was originally identified as a translational regulator in Caenorhabditis elegans that binds RNA [ 5 , 6 ]. MEX3A has been previously reported to act as oncogene in a variety of cancers, such as breast cancer [ 6 ], CRC [ 7 ] and osteosarcoma [ 8 ]. For example, Liang et al [ 9 ] found that MEX3A promotes lung adenocarcinoma metastasis by down-regulating LAMA2 and then activating PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

“…In the CRC study, Li et al [ 10 ] found that MEX3A benefits CRC tumorigenesis through RAP1/MAPK signaling. Zhou et al [ 7 ] revealed that MEX3A knockdown inhibits CRC tumorigenesis by up-regulating CDK2 expression. In conclusion, MEX3A is critical to CRC progression, but no studies have reported the role of MEX3A in CRC angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

MEX3A promotes angiogenesis in colorectal cancer via glycolysis

Zhou

et al. 2023

Libyan Journal of Medicine

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As a gastrointestinal malignancy, colorectal cancer (CRC) is a main cause of cancer-related deaths worldwide. Mex-3 RNA-binding family member A (MEX3A) is upregulated in multiple types of tumors and plays a critical role in tumor proliferation and metastasis. However, the function of MEX3A in CRC angiogenesis has not been fully understood. Hence, the aim of this study was to explore the role of MEX3A in CRC angiogenesis and investigate its underlying mechanisms. MEX3A expression in CRC was first investigated by bioinformatics means and then measured by qRT-PCR and Western blot. CCK-8 assay was employed to test cell viability. Angiogenesis assay was used to assess angiogenesis. The protein levels of VEGF, FGF and SDF-1 were evaluated using Western blot. The expression levels of MYC, HK2 and PGK1 were investigated by qRT-PCR. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were determined by Seahorse XP 96. The levels of pyruvate, lactate, citric acid and malate were measured by corresponding kits. Bioinformatics analysis demonstrated high MEX3A expression in CRC tissues and MEX3A enrichment in glycolysis and angiogenesis pathways. Cell assays showed high MEX3A expression in CRC cells and its promoting effects in CRC cell proliferation and glycolysis as well as angiogenesis. Rescue experiment confirmed that glycolysis inhibitor 2-DG could offset the promoting effects of MEX3A on the proliferation, angiogenesis and glycolysis of CRC cells. In conclusion, MEX3A could facilitate CRC angiogenesis by activating the glycolytic pathway, suggesting that MEX3A may be a novel therapeutic target for CRC.

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“…Furthermore, recent reports have implicated MEX3A as an oncogene that promotes tumor growth and cancer cell invasion in a variety of cancers such as lung, breast and cervical cancer 20 - 22 . In addition, in vitro assays showed that MEX3A promotes the migration, invasion and proliferation of CRC cells 23 , 24 . However, it is still unknown of the function and molecular mechanism of MEX3A in coordinating self-renewal and differentiation signals in CRC.…”

Section: Introductionmentioning

confidence: 99%

Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state

Yang¹,

Li²,

Tian³

et al. 2022

Theranostics

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Rationale: Dysregulation of signaling that governs self-renewal and differentiation of intestinal stem cells (ISCs) is a major cause of colorectal cancer (CRC) initiation and progression. Methods: qRT-PCR, western blotting, in situ hybridization, immunohistochemistry and immunofluorescence assays were used to detect the expression levels of MEX3A, KLF4 and E2F3 in CRC tissues. The biological functions of MEX3A were studied using Mex3a knockout (KO) and intestinal epithelium specific conditional knockout (cKO) mice, AOM-DSS mouse colorectal tumor model, Apc floxed mouse tumor model and intestinal and tumor organoids. Transcriptomic RNA sequencing (RNA-seq), RNA crosslinking immunoprecipitation (CLIP) and luciferase reporter assays were performed to explore the molecular mechanisms of MEX3A. Results: RNA-binding protein MEX3A, a specific ISC marker gene, becomes ectopically upregulated upon CRC and its levels negatively correlate with patient survival prognosis. MEX3A functions as an oncoprotein that retains cancer cells in undifferentiated and proliferative status and it enhances their radioresistance to DNA damage. Mechanistically, a rate limiting factor of cellular proliferation E2F3 induces MEX3A, which in turn activates WNT pathway by directly suppressing expression of its pro-differentiation transcription factor KLF4. Knockdown of MEX3A with siRNA or addition of KLF4 agonist significantly suppressed tumor growth both by increasing differentiation status of cancer cells and by suppressing their proliferation. Conclusions: It identifies E2F3-MEX3A-KLF4 axis as an essential coordinator of cancer stem cell self-renewal and differentiation, representing a potent new druggable target for cancer differentiation therapy.

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MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

Cited by 6 publications

References 27 publications

Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification

Three molecular subtypes and a five‐gene signature for hepatocellular carcinoma based on m7G‐related classification

MEX3A promotes angiogenesis in colorectal cancer via glycolysis

Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state

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