Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature

Karimpour, Mina; Ravanbakhsh, Reyhaneh; Maydanchi, Melika; Rajabi, Ali; Azizi, Faezeh; Saber, Aly

doi:10.1016/j.biopha.2021.112190

Cited by 26 publications

(13 citation statements)

References 238 publications

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“…Increasing evidence has demonstrated that the dysregulation of lncRNAs contributes to enhanced proliferation, metastasis and drug resistance in lung cancer [9,39,40]. The aim of the present study was to investigate the biological function and the up-and downstream regulatory mechanisms of ZNRD1-AS1 in lung cancer.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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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“…In NSCLC, MALAT1 is highly expressed in primary tumors and tumors overexpressing it have a higher tendency to metastasize. 18 , 22 Highly efficient knockdown of MALAT1 using zinc finger nuclease-based technology confirmed that MALAT1 promotes metastasis in vitro and in vivo without affecting cell proliferation. 23–25 Conversely, the use of antisense oligonucleotides (ASOs) inhibits metastasis formation by reducing the expression level of MALAT1 in tumors and surrounding stromal cells.…”

Section: Introductionmentioning

confidence: 92%

Long Noncoding RNAs in Lung Cancer: From Disease Markers to Treatment Roles

Chen¹,

Xie²,

Yu³

2022

CMAR

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There is an urgent need to identify reliable biomarkers that can be used in early diagnosis, prognostication prediction and as possible therapeutic targets for lung cancer due to its current poor prognosis. Long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis. Issues involved in the biofunctions and regulatory mechanisms of oncogenic and tumor-suppressive lncRNAs in lung cancer are discussed. Some lncRNAs have shown good diagnostic value, especially in combination with conventional serum protein markers. The use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. The biomarker function of lncRNAs may also indirectly involved in tumor therapy as a reference to conventional therapy. Overall, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact.

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“…MALAT1 forms a fairly complex secondary structure with exposure of multiple miRNA-binding sites (McCown et al 2019 ). Its abnormal overexpression is associated with a higher risk of metastasis in lung cancer (Karimpour et al 2021 ). Interestingly, a substantially cytosolic localization of MALAT1 has been demonstrated in three colon cancer lines (HCT116, SW480, SW620) (Sun et al 2019b ), although this result will need to be confirmed in other cell lines and in CRC samples.…”

Section: Malat1 and Other Lncrnas Affecting The Level Of Ty...mentioning

confidence: 99%

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Matuszyk

2022

Mol Med

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Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

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Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature

Cited by 26 publications

References 238 publications

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

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

Long Noncoding RNAs in Lung Cancer: From Disease Markers to Treatment Roles

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

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