KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer

Qian, Lu‐Xi; Cao, Xiang; Du, Mengnan; Ma, Chengxian; Zhu, Hongming; Peng, Yi; Hu, Xinyu; He, Xia; Yin, Li

doi:10.1016/j.bbrc.2021.04.020

Cited by 19 publications

(16 citation statements)

References 24 publications

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“…In the present study, we were inspired by the systematic research of Li et al; they reported that IGF2BP1/2/3, YTHDF1/3, HNRNPA2B1, and VIRMA exhibited copy number variations in amplification across 33 cancer types. Given that we conducted a preliminary study on the function of IGF2BP3 as a tumor promoter in esophageal cancer [ 23 ], we aimed to elucidate the expression characteristics and biological functions of IGF2BP3 in NPC. This work provides a basis for developing a new method of tumor treatment from an m6A perspective.…”

Section: Discussionmentioning

confidence: 99%

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Peng

Yang

et al. 2022

Cell Death Discov.

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N6-Methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotic cells. IGF2BP3, a well-known m6A reader, is deregulated in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. In this work, IGF2BP3 was upregulated in NPC tissues and cells. The high level of IGF2BP3 was positively related to late clinical stages, node metastasis, and poor outcomes. Moreover, IGF2BP3 accelerated NPC cell tumor progression and metastasis in vitro and vivo. Upstream mechanism analyses indicated that the high expression of IGF2BP3 in head and neck tumors was mainly due to mRNA level amplification. Luciferase assay and chromatin immunoprecipitation assay (CHIP) depicted that MYC was effectively bound to the promoter of IGF2BP3, thereby improving its transcriptional activity. Results also showed that IGF2BP3 was not only positively correlated with KPNA2 expression but also modulated the expression of KPNA2. m6A RNA immunoprecipitation (MeRIP) and RNA stability experiments verified that silencing IGF2BP3 significantly inhibited the m6A modification level of KPNA2, thereby stabilizing the mRNA stability of KPNA2. Rescue experiments proved that the effect of inhibiting or overexpressing IGF2BP3 on NPC cells was partly reversed by KPNA2. Collectively, MYC-activated IGF2BP3 promoted NPC cell proliferation and metastasis by influencing the stability of m6A-modified KPNA2. Our findings offer new insights that IGF2BP3 may serve as a new molecular marker and potential therapeutic target for NPC treatment.

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Section: Discussionmentioning

confidence: 99%

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Peng

Yang

et al. 2022

Cell Death Discov.

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“…Further studies showed that KIF18A was associated with proliferation, migration, invasion and radiation resistance of esophageal carcinoma cells. IGF2BP3 regulates the progression of esophageal cancer by affecting the mRNA stability of KIF18A in EC cell lines ( 56 ).The protein and gene expression levels of miR-454-3p in ESCC tissues and cells were down-regulated compared with those in adjacent normal tissues and normal esophageal epithelial cells. In the mouse subcutaneous transplanted tumor model, miR-454-3p controls IGF2BP1 through ERK and AKT signaling pathways and inhibits the proliferation, migration and apoptosis of ESCA cells.…”

Section: Expression and Role Of Igf2bps In Hnsccmentioning

confidence: 99%

Role of IGF2BPs in head and neck squamous cell carcinoma

Chang²,

Li³

et al. 2022

Front. Oncol.

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IGF2BPs belongs to a family of conserved RNA-bound oncoembryonic proteins that play a crucial part in various aspects of cell function, such as cell migration, morphology, metabolism, proliferation and differentiation. Recent studies have shown that IGF2BPs play a role as a member of m6A reader. m6A is the most abundant modification in RNA epigenetics, which is closely related to a family of RNA-binding proteins. These proteins are fell into three categories—writers, readers and erasers. In the present study, IGF2BPs play an important role in tumor metabolism, especially in head and neck squamous cell carcinoma (HNSCC) metabolism. In this paper, the basic structure of IGF2BPs, its role in the development of HNSCC, molecular mechanism, research progress and research prospect of IGF2BPs in HNSCC are reviewed, which will providing new ideas for further study of IGF2BPs.

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“…Thus, the A allele of rs5746136 in SOD2 was associated with a reduced risk of bladder cancer [ 57 ]. m 6 A could deposit on various type of RNA, such as coding RNA and non-coding RNA, participate in all steps of RNA metabolism and post-transcriptionally regulate the expression of the gene ( Table 1 ) [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ].…”

Section: M 6 a Modification And Its Effect On Vari...mentioning

confidence: 99%

“…Compared to wild-type mice, YTHDF1 -/- mice acquired a better therapeutic efficacy of PD-L1 checkpoint blockade, implying the potential of YTHDF1 as a target of antitumor immunotherapy [ 150 ]. Similarly, m 6 A regulators played a non-negligible role in the therapeutic resistance of ESCA [ 67 , 77 , 122 , 129 , 151 ].…”

Section: The Role Of M 6 a Regulators In Developme...mentioning

confidence: 99%

The Role of m6A Modification and m6A Regulators in Esophageal Cancer

Niu

Wang

et al. 2022

Cancers

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N6-methyladenosine (m6A) modification, the most prevalent RNA modification, is involved in all aspects of RNA metabolism, including RNA processing, nuclear export, stability, translation and degradation. Therefore, m6A modification can participate in various physiological functions, such as tissue development, heat shock response, DNA damage response, circadian clock control and even in carcinogenesis through regulating the expression or structure of the gene. The deposition, removal and recognition of m6A are carried out by methyltransferases, demethylases and m6A RNA binding proteins, respectively. Aberrant m6A modification and the dysregulation of m6A regulators play critical roles in the occurrence and development of various cancers. The pathogenesis of esophageal cancer (ESCA) remains unclear and the five-year survival rate of advanced ESCA patients is still dismal. Here, we systematically reviewed the recent studies of m6A modification and m6A regulators in ESCA and comprehensively analyzed the role and possible mechanism of m6A modification and m6A regulators in the occurrence, progression, remedy and prognosis of ESCA. Defining the effect of m6A modification and m6A regulators in ESCA might be helpful for determining the pathogenesis of ESCA and providing some ideas for an early diagnosis, individualized treatment and improved prognosis of ESCA patients.

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KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer

Cited by 19 publications

References 24 publications

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Role of IGF2BPs in head and neck squamous cell carcinoma

The Role of m6A Modification and m6A Regulators in Esophageal Cancer

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