MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting

Bhat, Asif Ahmad; Afzal, Obaid; Afzal, Muhammad; Gupta, Gaurav; Thapa, Riya; Ali, Haider; Hassan almalki, Waleed; Kazmi, Imran; Alzarea, Sami I.; Saleem, Shakir; Samuel, Vijaya Paul; Gubbiyappa, Shiva Kumar; Subramaniyan, Vetriselvan

doi:10.1016/j.prp.2023.154991

Cited by 12 publications

(3 citation statements)

References 88 publications

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“…We utilized MALAT1-targeting antisense oligonucleotides (MALAT1 ASOs) in our in vivo study to evaluate their therapeutic potential for lung cancer treatment. This approach is bolstered by the existing literature demonstrating the efficacy of MALAT1 ASOs in significantly reducing MALAT1 levels, which are known to contribute to cancer progression [8]. Given the role of MALAT1 in promoting cell proliferation and metastasis, particularly in lung cancer, targeting this lncRNA represents a promising therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

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Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment

Li,

Dhilipkannah,

Holden

et al. 2024

Cancers

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African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs), longer than 200 nucleotides in length, play pivotal roles in various aspects of cancer development, progression, and metastasis [8]. LncRNAs are a crucial regulatory layer in lung cancer, playing diverse roles in driving the tumorigenesis [9,10].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment

Li,

Dhilipkannah,

Holden

et al. 2024

Cancers

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“…Although BC200 is known to be highly expressed in dendrites and is thought to be involved in local translational regulation [ 38 , 39 ] and BCYRN1 has been shown to be involved in epilepsy, Alzheimer’s disease, and cognitive function of multiple sclerosis [ 40 , 41 , 42 ], BCYRN1 is known to exhibit high expression in several cancer types, such as non-small-cell lung cancer [ 43 , 44 , 45 ], gastric cancer [ 46 , 47 , 48 ], colorectal carcinoma [ 49 , 50 , 51 ], NK/T-cell lymphoma [ 52 ], and glioblastoma [ 53 ]. Additionally, abundant BCYRN1 promotes cancer metastasis and progression by adsorbing microRNAs “like a sponge” [ 54 ]. Knockdown of the lncRNA BCYRN1 using small interfering RNA (siRNA) reduces cell viability in several types of cancer [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer

Arima,

Yoshino,

Fukumoto

et al. 2024

IJMS

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Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

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Targeting the autophagy-miRNA axis in prostate cancer: toward novel diagnostic and therapeutic strategies

Syed,

Alshammari,

Banu

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting

Cited by 12 publications

References 88 publications

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment

LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer

Targeting the autophagy-miRNA axis in prostate cancer: toward novel diagnostic and therapeutic strategies

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