ALKBH5‐mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9

Li, Yushan; Yan, Bingrui; Wang, Xin; Li, Qiuying; Kan, Xuan; Wang, Jingting; Sun, Yanan; Wang, Peng; Tian, Linli; Liu, Ming

doi:10.1111/jcmm.17091

Cited by 30 publications

(20 citation statements)

References 36 publications

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“…For example, the lncRNA UBA6-AS1 inhibits the decay of UBA6 mRNA by modifying the methylation status of m6A, thus suppressing ovarian cancer cell malignancy [ 16 ]. The m6A demethylase ALKBH5 mediates the modification of the methylation of the lncRNA KCNQ1OT1, thus upregulating the expression of the HOXA9 gene and promoting the development of laryngeal squamous cell carcinoma [ 17 ]. Nevertheless, previous studies have focused primarily on m6A methylation.…”

Section: Introductionmentioning

confidence: 99%

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Zhu

Kong

et al. 2022

BioMed Research International

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Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

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Section: Introductionmentioning

confidence: 99%

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Zhu

Kong

et al. 2022

BioMed Research International

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“…With the continuous deepening of lncRNA research, there have been more and more studies on lncRNA methylation modification in recent years. Li et al [ 37 ] investigated the role and mechanism of m6A modification of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) in the progression of laryngeal squamous cell carcinoma (LSCC), suggesting that ALKBH5-mediated m6A modification of KCNQ1OT1 is triggered by the upregulation of HOXA9 LSCC development. Liu et al [ 38 ] identified the differentially expressed lncRNA in gastric cancer and found that the m6A modification of THAP7-AS1 by METTL3 enhanced its expression, and its high expression was associated with positive lymph node metastases and a poor prognosis in patients with gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

5-Methylcytosine-Related Long Noncoding RNAs Are Potential Biomarkers to Predict Overall Survival and Regulate Tumor-Immune Environment in Patients with Bladder Cancer

Wang

Chen

et al. 2022

Disease Markers

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The role of 5-methylcytosine-related long noncoding RNAs (m5C-lncRNAs) in bladder cancer (BLCA) remains unclear. Here, we aim to study the prognostic value, gene expression characteristics, and correlation between the m5C-lncRNA risk model and the tumor microenvironment, immune infiltration, and tumor mutations in BLCA. After collecting BLCA patient RNA sequence transcriptome data, clinical information and mutation data from the Cancer Genome Atlas (TCGA) database, 17 m5C-related lncRNAs independently correlated with OS were obtained by Lasso and multivariate Cox regression analysis, and a risk model was constructed. Univariate Cox, multivariate Cox regression analysis, and the C-index curve proved that the risk model was a significant independent prognostic indicator for patients with BLCA. ESTIMATE and CIBERSORT indicated that the higher the number of immune cells and stromal cells in TME, the higher the prognostic risk. We found that in the low-risk group, the expression levels of immune cells that predicted a good prognosis were higher, including plasma cells, regulatory T cells, and CD 8 T cells. There is a negative correlation between TMB and risk score. The TMB of the low-risk group is significantly higher than that of the high-risk group. In conclusion, the m5C-related risk model is crucial to predict the prognosis of patients with BLCA.

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“…Another study showed that ALKBH5-mediated m6A demethylation of the lncRNA RMRP plays an oncogenic role in lung adenocarcinoma [ 25 ]. It has also been shown that ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 regulates the development of LSCC [ 63 ], and that ALKBH5-mediated m6A modification of PVT1 promotes the progression of OS [ 51 ]. The two studies also showed YTHDF2 could recognize m6A-modified sites of lncRNA KCNQ1OT1 or PVT1 and regulate their stability [ 51 , 63 ], but whether ALKBH5 regulates the stability of PVT1 via YTHDF2 in lung cancer cells remains to be examined further.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown that ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 regulates the development of LSCC [ 63 ], and that ALKBH5-mediated m6A modification of PVT1 promotes the progression of OS [ 51 ]. The two studies also showed YTHDF2 could recognize m6A-modified sites of lncRNA KCNQ1OT1 or PVT1 and regulate their stability [ 51 , 63 ], but whether ALKBH5 regulates the stability of PVT1 via YTHDF2 in lung cancer cells remains to be examined further. Further, we also showed that a serious tumor-related genes could be regulated by ALKBH5-PVT1 axis, but the functional evidence is still lacking.…”

Section: Discussionmentioning

confidence: 99%

The RNA demethylase ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the stability of the LncRNA PVT1

Shen

Zuo

et al. 2022

Cancer Cell Int

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Background N6-methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in human cancer progression. However, the biological function of m6A methylation requires further studied in cancer, especially in tumor angiogenesis. Methods A public database was used to analyze the expression and overall survival of ALKBH5 and PVT1 in lung cancer patients. CCK-8 and colony formation assays were performed to detect cell proliferation, a transwell assay was used to assess cell migration, and a tube formation assay was performed to assess angiogenic potential in vitro. A zebrafish lung cancer xenograft model was used to verify the function of ALKBH5 and PVT1 in vivo. Western blot assays were used to measure the relative protein expression in lung cancer cells. SRAMP predictor analysis and RNA stability experiments were used to examine the potential m6A modification. Results Bioinformatics analysis showed that the expression levels of m6A-related genes were changed significantly in lung cancer tissues compared with normal lung tissues. We then identified that ALKBH5 was upregulated in lung cancer tissues and associated with poor prognosis of lung cancer patients by analyzing a public database. Knockdown of ALKBH5 inhibited the proliferation and migration of cultured lung cancer cell lines. Zebrafish lung cancer xenografts showed that ALKBH5 silencing also suppressed the growth and metastasis of lung cancer cells. Moreover, knockdown of ALKBH5 inhibited the angiogenesis of lung cancer in vitro and in vivo. Mechanistic studies showed that knockdown of ALKBH5 decreased the expression and stability of PVT1 in lung cancer cells. We next observed that PVT1 promoted the progression of lung cancer cells in vitro and in vivo and regulated the expression of VEGFA and angiogenesis in lung cancer. Finally, rescue experiments revealed that ALKBH5 regulated the proliferation, migration and angiogenesis of lung cancer cells, partially through PVT1. Conclusion Our results demonstrate that ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the expression and stability of PVT1, which provides a potential prognostic and therapeutic target for lung cancer patients.

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ALKBH5‐mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9

Cited by 30 publications

References 36 publications

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

5-Methylcytosine-Related Long Noncoding RNAs Are Potential Biomarkers to Predict Overall Survival and Regulate Tumor-Immune Environment in Patients with Bladder Cancer

The RNA demethylase ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the stability of the LncRNA PVT1

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