On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Lara-Lemus, Roberto

doi:10.7150/jca.30376

Cited by 19 publications

(23 citation statements)

References 88 publications

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“…Moreover, some studies claimed that IL-1β could promote functional recovery, Schwann cell proliferation, and neurite outgrowth (Temporin et al, 2008;Nadeau et al, 2011). Emerging studies indicated that MAL was implicated in tumor promotion and suppression (Lara-Lemus, 2019). Importantly, overexpression of MAL could impede myelination in the PNS, which was consistent with our results (Buser et al, 2009;Schmid et al, 2014).…”

Section: Discussionsupporting

confidence: 90%

Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

Yin

Peng

Ying

et al. 2021

Front. Cell Dev. Biol.

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Peripheral nerve injury (PNI) is a common clinical problem, which can cause severe disability and dramatically affect a patient’s quality of life. Neural regeneration after PNI is a complex biological process that involves a variety of signaling pathways and genes. Emerging studies demonstrated that long non-coding RNAs (lncRNAs) were abnormally expressed after PNI and played pivotal roles in peripheral nerve regeneration. Based on the rat sciatic nerve injury model, we found that the expression levels of several lncRNAs were increased significantly in the sciatic nerve after injury. Software prediction prompted us to focus on one up-regulated lncRNA, MSTRG.24008.1. Dual-luciferase reporter assay, RNA pull-down assay and RNA interference approach verified that MSTRG.24008.1 regulated neuroregeneration via the miR-331-3p/nucleotide-binding oligomerization domain-like pyrin domain containing 3 (NLRP3)/myelin and lymphocyte protein (MAL) axis in vitro. Subsequently, we performed gastrocnemius muscle gravity and sciatic functional index experiments to evaluate the recovery of injured sciatic nerves after MSTRG.24008.1 siRNA interference in vivo. In conclusion, knockdown of MSTRG.24008.1 promotes the regeneration of the sciatic nerve via the miR-331-3p/NLRP3/MAL axis, which may provide a new strategy to evaluate and repair injured peripheral nerves clinically.

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Section: Discussionsupporting

confidence: 90%

Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

Yin

Peng

Ying

et al. 2021

Front. Cell Dev. Biol.

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“…It is clear is that the proposed role of MAL as a tumor suppressor does not extend to all types of cancer, and malignancies of hematological cell types in which MAL is endogenously expressed, and at least those of the ovarian epithelium, are specifically excluded. MAL may have a tumor suppressive role in some cancers and an oncogenic role in others [ 293 ]. However, there is no direct evidence of such an oncogenic role, since the link between high levels of MAL correlate and the poor prognosis of B-cell lymphomas and ovarian cancer [ 226 , 227 ] does not necessarily mean that MAL induces the transformation of normal cells in neoplastic cells.…”

Section: Mal In Cancermentioning

confidence: 99%

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Rubio-Ramos

Labat-de-Hoz

Correas

et al. 2021

Cells

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The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

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“…It participates in the apical transport of proteins in polarized epithelial cells [ 7 ]. The role of its abnormal expression in tumorigenesis and development has attracted increasing attention [ 8 ]. MAL is specifically expressed in different tissues and cells, and its expression level differs in different cells of normal gastric tissue [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

MAL protein suppresses the metastasis and invasion of GC cells by interfering with the phosphorylation of STAT3

Geng

et al. 2022

J Transl Med

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Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide and is accompanied by low diagnosis and survival rates. The molecular mechanism of GC must be elucidated to improve treatment strategies. Recent research has shown that the expression of myelin and lymphocyte (MAL) protein is reduced in a variety of adenocarcinomas and has the function of suppressing tumor growth. However, the mechanism by which MAL regulates the epithelial-mesenchymal transition (EMT) in GC remains unclear. Here, we showed that MAL expression was downregulated in specimens from patients with GC and was negatively correlated with the clinical stage. Gain- and loss-of function assays showed that interference with MAL significantly increased tumor cell proliferation, metastasis, invasion and the EMT. Overexpression of MAL significantly inhibited the malignant behavior of GC cells. Moreover, MAL suppressed the malignant behavior of GC cells by inhibiting STAT3 phosphorylation in vitro and in vivo. Our data indicate that MAL suppresses the malignant behavior of GC cells via the STAT3/EMT axis. This study also provides insights into the pathophysiological process of GC and a reference for diagnosis and treatment.

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On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Cited by 19 publications

References 88 publications

Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

Long Non-coding RNA MSTRG.24008.1 Regulates the Regeneration of the Sciatic Nerve via the miR-331-3p–NLRP3/MAL Axis

The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

MAL protein suppresses the metastasis and invasion of GC cells by interfering with the phosphorylation of STAT3

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