Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer

Chen, Changhao; Luo, Yuming; Wang, He; Zhao, Yue; Kong, Yao; Liu, Hongwei; Zhong, Guangzheng; Li, Yuting; Li, Jun; Huang, Jian; Chen, Rufu; Lin, Tianxin

doi:10.1172/jci130892

Cited by 299 publications

(263 citation statements)

References 48 publications

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“…It is reported that HNRNPA2B1 could selectively bind to m 6 A-containing transcripts via the “m 6 A-switch,” a mechanism in which m 6 A weakens Watson–Crick base pairing to destabilize the RNA hairpin structure and thereby exposes the single stranded hnRNP binding motif ( 37 ). HNRNPA2B1 has been reported to be a RNA-binding protein involved in different cancer progression ( 38 – 40 ). HNRNPA2B1 could interact with LINC01234 to promote lung cancer progression ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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N6-methyladenosine (m 6 A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m 6 A modification and m 6 A RNA methylation regulators were involved in cancer progression. However, the m 6 A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m 6 A regulators using The Cancer Genome Atlas data and found 14 of 19 m 6 A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m 6 A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m 6 A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m 6 A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

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Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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“…Recently, a growing number of evidence has showed that many lncRNAs play important regulatory roles in diverse biological processes of BC, such as BLACAT2, LNMAT1, LNMAT2, PTENP1, UCA-1, HOTAIR, and etc. [11][12][13][14][15][16][17][18]. Cancer susceptibility candidate 9 (CASC9, Gene ID 101805492 in NCBI records) is a novel identified lncRNA located at 8q21.11 [19].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer

Zhan

Zhang

et al. 2020

J Exp Clin Cancer Res

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Background: Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long noncoding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown. Methods: Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9. Results: This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/β-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis. Conclusion: In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.

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“…Gastric cancer cells produce and secrete the exosomal HOXA distal transcript antisense RNA (HOTTIP) and it is superior to traditional biomarkers in the serum of cancer patients, such as cancer embryonic antigen (CEA), cancer antigen 19-9 and cancer antigen 72-4 [94]. The lymph node metastasis-associated transcript 2 (LNMAT2) increases lymphatic metastasis in bladder cancer, most likely by binding to the prospero homeobox 1(PROX1) promoter, where it regulates PROX1 transcription by inducing hnRNPA2B1-mediated H3 lysine 4 trimethylation, resulting in lymphangiogenesis and lymphatic metastasis [95]. Exosomes can also be affected by lncRNAs.…”

Section: Emt and Exosomal Lncrna In Cancermentioning

confidence: 99%

Long non-coding RNAs regulate drug resistance in cancer

et al. 2020

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Chemoresistance, whether intrinsic or acquired, is a major obstacle in the treatment of cancer. The resistance of cancer cells to chemotherapeutic drugs can result from various mechanisms. Over the last decade, it has been reported that 1ong noncoding RNAs (lncRNAs) can mediate carcinogenesis and drug resistance/sensitivity in cancer cells. This article reviews, in detail, recent studies regarding the roles of lncRNAs in mediating drug resistance.

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Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer

Cited by 299 publications

References 48 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer

Long non-coding RNAs regulate drug resistance in cancer

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