RNA polymerase I subunit 12 plays opposite roles in cell proliferation and migration

Yin, Xiaomei; Zhang, Kewei; Wang, Juan; Zhou, Xiangyu; Zhang, Cheng; Song, Xiaoye; Wu, Zhenpeng; Du, Jiannan; Chen, Qi‐Yue; Zhang, Shihua; Deng, Wensheng

doi:10.1016/j.bbrc.2021.04.091

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…A previous study reported that ZNRD1 expression was increased in hepatocellular carcinoma and that ZNRD1 knockdown inhibited cell proliferation, migration and invasion in vitro, as well as tumor growth in vivo [41]. However, the number of studies involving ZNRD1-AS1 is limited and ZNRD1 has more frequently been described as a tumor suppressor gene and has been determined to be highly expressed in tumors [11][12][13]. For example, in cervical and endometrial cancer, ZNRD1-AS1 can serve a pro-proliferative and migratory role via the downregulation of ZNRD1 [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…For example, the lncRNA HOX transcript antisense RNA is able to repress gene expression by recruiting chromatin modifiers and can promote lung cancer cell proliferation, migration, invasion and drug resistance [9]. Moreover, zinc ribbon domain-containing 1 (ZNRD1)-antisense 1 (AS1) encodes a protein that potentially contributes to the progression of cancer and HIV infection [10,11]. Previous studies have demonstrated that ZNRD1-AS1 is upregulated and is described as an oncogene in several types of cancer, including liver, cervical and endometrial cancers [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, zinc ribbon domain-containing 1 (ZNRD1)-antisense 1 (AS1) encodes a protein that potentially contributes to the progression of cancer and HIV infection [10,11]. Previous studies have demonstrated that ZNRD1-AS1 is upregulated and is described as an oncogene in several types of cancer, including liver, cervical and endometrial cancers [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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lncRNA ZNRD1-AS1 promotes malignant lung cell proliferation, migration, and angiogenesis via the miR-942/TNS1 axis and is positively regulated by the m6A reader YTHDC2

Wang

Tan

et al. 2022

Mol Cancer

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Rationale Lung cancer is the most prevalent form of cancer and has a high mortality rate, making it a global public health concern. The N6-methyladenosine (m6A) modification is a highly dynamic and reversible process that is involved in a variety of essential biological processes. Using in vitro, in vivo, and multi-omics bioinformatics, the present study aims to determine the function and regulatory mechanisms of the long non-coding (lnc)RNA zinc ribbon domain-containing 1-antisense 1 (ZNRD1-AS1). Methods The RNAs that were bound to the m6A ‘reader’ were identified using YTH domain-containing 2 (YTHDC2) RNA immunoprecipitation (RIP)-sequencing. Utilizing methylated RIP PCR/quantitative PCR, pull-down, and RNA stability assays, m6A modification and ZNRD1-AS1 regulation were analyzed. Using bioinformatics, the expression levels and clinical significance of ZNRD1-AS1 in lung cancer were evaluated. Using fluorescent in situ hybridization and quantitative PCR assays, the subcellular location of ZNRD1-AS1 was determined. Using cell migration, proliferation, and angiogenesis assays, the biological function of ZNRD1-AS1 in lung cancer was determined. In addition, the tumor suppressor effect of ZNRD1-AS1 in vivo was validated using a xenograft animal model. Through bioinformatics analysis and in vitro assays, the downstream microRNAs (miRs) and competing endogenous RNAs were also predicted and validated. Results This study provided evidence that m6A modification mediates YTHDC2-mediated downregulation of ZNRD1-AS1 in lung cancer and cigarette smoke-exposed cells. Low levels of ZNRD1-AS1 expression were linked to adverse clinicopathological characteristics, immune infiltration, and prognosis. ZNRD1-AS1 overexpression was shown to suppress lung cancer cell proliferation, migration, and angiogenesis in vitro and in vivo, and to reduce tumor growth in nude mice. ZNRD1-AS1 expression was shown to be controlled by treatment of cells with either the methylation inhibitor 3-Deazaadenosine or the demethylation inhibitor Meclofenamic. Furthermore, the miR-942/tensin 1 (TNS1) axis was demonstrated to be the downstream regulatory signaling pathway of ZNRD1-AS1. Conclusions ZNRD1-AS1 serves an important function and has clinical relevance in lung cancer. In addition, the findings suggested that m6A modification could mediate the regulation of the ZNRD1-AS1/miR-942/TNS1 axis via the m6A reader YTHDC2. Graphical Abstract

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