HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway

Guo, Cheng-Ming; Chu, Hongjin; Gong, Zhaohui; Zhang, Bo; Li, Chen; Chen, Jian; Huang, Lei

doi:10.1016/j.lfs.2021.119522

Cited by 27 publications

(21 citation statements)

References 41 publications

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“…IGF1R increases the proliferation and glycolysis of pancreatic cancer 28 . HOXB13 accelerates gastric cancer cell migration and invasion by upregulating the expression of IGF1R 29 . IGF1R is activated through miR‐122 downregulation, resulting in activation of the RAS/RAF/ERK pathway in HCC 30 .…”

Section: Discussionmentioning

confidence: 99%

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Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis

Shen

Zhao

Zeng

et al. 2022

Annals of the New York Academy of Sciences

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An increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR-6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelialto-mesenchymal transition, which could be rescued by treatment with a miR-6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR-6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.

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Section: Discussionmentioning

confidence: 99%

“… 28 HOXB13 accelerates gastric cancer cell migration and invasion by upregulating the expression of IGF1R. 29 IGF1R is activated through miR‐122 downregulation, resulting in activation of the RAS/RAF/ERK pathway in HCC. 30 Based on these data, we examined the expression of IGF1R in HCC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis

Shen

Zhao

Zeng

et al. 2022

Annals of the New York Academy of Sciences

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“…9 In contrast, Guo et al demonstrated that HOXB13 expression promotes the proliferation, migration, and invasion of gastric cancer cells by PI3 K/AKT/mTOR signaling via IGF-1R2. 4 Such contradictory phenomena were also found in CRC. A study to analyze the expression of the paralogous 13 HOX genes in proximal and distal CRC patients revealed that HOXB13 showed a statistical association with lymph nodes metastasis and was overexpressed in right CRC tissues.…”

Section: Discussionmentioning

confidence: 92%

Expression profile and prognostic significance of HOXB13 in rectal cancer

et al. 2022

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Background This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer. Methods HOXB13 expression in rectal cancer and normal adjacent tissues was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, and its clinicopathological characteristics and prognosis were statistically tested. Furthermore, we evaluated the association between tumor immune infiltrating cells and HOXB13 using the tumor immune estimation resource (TIMER) database. The potential biological mechanism associated with HOXB13 overexpression was investigated by gene set enrichment analysis (GSEA). Results The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues ( P < 0.05). HOXB13 expression was significantly correlated with depth of invasion, lymphatic invasion, lymph node metastasis, distant metastasis, and pathological tumor node metastasis stage ( P < 0.05). Kaplan–Meier survival curves confirmed that HOXB13 overexpression was correlated negatively with overall survival and disease-free survival in rectal cancer ( P < 0.05). Also, multivariate Cox regression analysis demonstrated that HOXB13 expression, age, and lymphatic invasion were independent prognostic factors in rectal cancer ( P < 0.05). Plus, the results from the TIMER database indicated that HOXB13 expression has a significant association with several immune cell infiltrates. Finally, the GSEA results indicated that HOXB13 participated in the various immune-associated processes, including natural killer cell-mediated cytotoxicity and the T-cell receptor signaling pathway. Conclusion Our study showed an essential role of HOXB13 in rectal cancer immunity and prognosis. Significantly, the overexpression of HOXB13 leads to the worse prognosis for patients with rectal cancer, which will contribute to understanding molecular mechanisms associated with tumor pathogenesis and prognosis in this disease.

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“…In gastric cancer, a reduction of FTO protein level is associated with poor prognosis suggesting an anti-oncogenic role of FTO in this cancer 74 . However, this discovery remains controversial, as another study found FTO to be upregulated in gastric cancer 75 . Investigation of the prognosis value of FTO revealed its anti-oncogenic function in lung cancer.…”

Section: ‘Context-dependent’ Function Of Fto In Cancermentioning

confidence: 99%

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

2022

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The last decade has seen mRNA modification emerge as a new layer of gene expression regulation. The Fat mass and obesity-associated protein (FTO) was the first identified eraser of N6-methyladenosine (m6A) adducts, the most widespread modification in eukaryotic messenger RNA. This discovery, of a reversible and dynamic RNA modification, aided by recent technological advances in RNA mass spectrometry and sequencing has led to the birth of the field of epitranscriptomics. FTO crystallized much of the attention of epitranscriptomics researchers and resulted in the publication of numerous, yet contradictory, studies describing the regulatory role of FTO in gene expression and central biological processes. These incongruities may be explained by a wide spectrum of FTO substrates and RNA sequence preferences: FTO binds multiple RNA species (mRNA, snRNA and tRNA) and can demethylate internal m6A in mRNA and snRNA, N6,2′-O-dimethyladenosine (m6Am) adjacent to the mRNA cap, and N1-methyladenosine (m1A) in tRNA. Here, we review current knowledge related to FTO function in healthy and cancer cells. In particular, we emphasize the divergent role(s) attributed to FTO in different tissues and subcellular and molecular contexts.

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HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway

Cited by 27 publications

References 41 publications

Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis

Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis

Expression profile and prognostic significance of HOXB13 in rectal cancer

The multifaceted functions of the Fat mass and Obesity-associated protein (FTO) in normal and cancer cells

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