Cited by 54Cancer-related molecular mechanisms researchMicroRNA in disease regulationRNA modifications and cancer

LncRNA NUTM2A‐AS1 positively modulates TET1 and HIF‐1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR‐376a

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Wang, Ji, Yu, Ziyang, Wang, Jun, Shen, Yidan, Qiu, Junlan, Zhuang, Zhixiang·2020·Cancer Medicine

Abstract

Long noncoding RNA NUTM2A‐AS1 has been shown to be dysregulated in non‐small cell lung carcinoma. To date, it is unclear whether NUTM2A‐AS1 plays a role in gastric cancer progression. The purpose of this study is to elucidate the molecular mechanism of the role of NUTM2A‐AS1 in gastric cancer. mRNA and protein levels were measured by RT‐qPCR and western blot methods. Invasion ability was examined by transwell assay. Cell viability was determined by MTT assay. Dual‐luciferase assay, RNA pull down, and RNA immunoprecipitation were used to confirm direct binding of between miR‐376a and NUTM2A‐AS1 or TET1. Xenografting tumor assay and TCGA analysis showed the contributory role of NUTM2A‐AS1 in vivo and human clinical setting. Our results suggested that NUTM2A‐AS1 promoted cell viability, invasion, and drug resistance of gastric cancer cells, which was largely rescued by miR‐376a. More interestingly, TET1 and HIF‐1A were negatively regulated by miR‐376a. TET1 could interact with HIF‐1A to modulate PD‐L1. Finally, we revealed that PD‐L1 was key to NUTM2A‐AS1‐ and miR‐376a‐mediated tumorigenesis and drug resistance. In summary, our conclusions facilitate us understand the underlying mechanism and develop novel treatment strategy for gastric cancer.

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  • Various critical transcription factors, including HIF-1α, c-MYC, NF-kB, STAT3, c-JUN, and miR-138-5p, have been shown to transcriptionally regulate PD-L1 expression.

    “Various critical transcription factors, including HIF-1α, c-MYC, NF-kB, STAT3, c-JUN, and miR-138-5p have been shown to transcriptionally regulate PD-L1 expression25–30.”

    From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [25]

    The Results section ('TET1 interacts with HIF-1A to regulate PD-L1'; page unavailable) reports that HIF-1A enhanced PD-L1 expression in gastric cancer cells. The copy does not establish PD-L1 regulation by the other listed factors—c-MYC, NF-kB, STAT3, c-JUN, or miR-138-5p—so it supports only the HIF-1α part of the sentence. (LLM, conf=0.88)

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References 39 · Cited by 54

Authors
Wang, J., Yu, Z., Wang, J., Shen, Y., Qiu, J., & Zhuang, Z.
Affiliations
  • Second Affiliated Hospital of Soochow University (CN)
  • Suzhou Science and Technology Town Hospital (CN)
Corresponding author
Zhuang, Zhixiang
Venue
Cancer Medicine
Publisher
Wiley
Published
2020-10-22
Volume
9
Issue
24
Pages
9499-9510
ISSN
2045-7634 (ISSN-L)
OpenAlex
W3093607399
Cited by
54
References
39
Citations by year
2026: 3 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 12 · 2021: 8
FWCI
2.48
Type
journal article
Language
en
Open access
Locations
  • Cancer Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81603181)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
long non-coding RNA, miR-376a, TET1, HIF1A, PD-L1, gastric cancer, drug resistance, carcinogenesis, cell invasion, microRNA sponge
MeSH terms
Animals, Cell Movement, Humans, Mixed Function Oxygenases, Proto-Oncogene Proteins, Stomach Neoplasms, Survival Rate, Mice, SCID, Mice, Inbred NOD, Apoptosis, Drug Resistance, Neoplasm, Databases, Genetic, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, B7-H1 Antigen, RNA, Long Noncoding, Heterografts

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