HuR as Therapeutic Target in Cancer: What the Future Holds

Goutas, Dimitrios; Pergaris, Alexandros; Giaginis, Constantinos; Theocharis, Stamatios

doi:10.2174/0929867328666210628143430

Cited by 20 publications

(21 citation statements)

References 57 publications

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“…Before ELAVL1 was recognized as an m6A regulator, ELAVL1, as a traditional RNA-binding protein, was found to be involved in the occurrence and progression of almost all tumors ( 58 , 59 ). With the development of m6A research, ELAVL1, as an m6A regulator, was found to interact with other m6A regulators to regulate RNA metabolism ( 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

Cai

Bai

et al. 2022

Front. Oncol.

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N6-Methyladenosine (m6A) imbalance is an important factor in the occurrence and development of prostate cancer (PCa). Many m6A regulators have been found to be significantly dysregulated in PCa. ELAVL1 is an m6A binding protein that can promote the occurrence and development of tumors in an m6A-dependent manner. In this study, we found that most m6A regulators were significantly dysregulated in PCa, and some m6A regulators were associated with the progression-free interval. Mutations and copy number variations of these m6A regulators can alter their expression. However, ELAVL1 mutations were not found in PCa. Nevertheless, ELAVL1 upregulation was closely related to PCa proliferation. High ELAVL1 expression was also related to RNA metabolism. Further experiments showed that ELAVL1 interacted with other m6A regulators and that several m6A regulatory mRNAs have m6A sites that can be recognized by ELAVL1. Additionally, protein–protein interactions occur between ELAVL1 and other m6A regulators. Finally, we found that the dysregulation of ELAVL1 expression occurred in almost all tumors, and interactions between ELAVL1 and other m6A regulators also existed in almost all tumors. In summary, ELAVL1 is an important molecule in the development of PCa, and its interactions with other m6A regulators may play important roles in PCa progression.

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Section: Discussionmentioning

confidence: 99%

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

Cai

Bai

et al. 2022

Front. Oncol.

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“…Several miRNAs regulating HuR expression have been identified in human cancers. Although HuR expression is increased in most neoplasms [ 160 ], this knowledge is limited to certain types of cancers and has essentially been demonstrated in vitro using cancer cell lines.…”

Section: Mirnas-regulating Hur and Ttp Family Membersmentioning

confidence: 99%

MicroRNAs, Tristetraprolin Family Members and HuR: A Complex Interplay Controlling Cancer-Related Processes

Sobolewski

Dubuquoy

Legrand

2022

Cancers

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MicroRNAs represent the most characterized post-transcriptional regulators of gene expression. Their altered expression importantly contributes to the development of a wide range of metabolic and inflammatory diseases but also cancers. Accordingly, a myriad of studies has suggested novel therapeutic approaches aiming at inhibiting or restoring the expression of miRNAs in human diseases. However, the influence of other trans-acting factors, such as long-noncoding RNAs or RNA-Binding-Proteins, which compete, interfere, or cooperate with miRNAs-dependent functions, indicate that this regulatory mechanism is much more complex than initially thought, thus questioning the current models considering individuals regulators. In this review, we discuss the interplay existing between miRNAs and the AU-Rich Element Binding Proteins (AUBPs), HuR and tristetraprolin family members (TTP, BRF1 and BRF2), which importantly control the fate of mRNA and whose alterations have also been associated with the development of a wide range of chronic disorders and cancers. Deciphering the interplay between these proteins and miRNAs represents an important challenge to fully characterize the post-transcriptional regulation of pro-tumorigenic processes and design new and efficient therapeutic approaches.

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“…HuR overexpression has been repeatedly linked to malignant transformation, and increased nuclear/cytoplasmic HuR expression has been associated with patients' prognosis in different malignancies [21]. The above-mentioned properties advocate for the adverse clinical outcomes related to HuR protein overexpression in various cancer types, including advanced stage, positive lymph nodes and poor survival [22][23][24][25][26][27].…”

Section: Hur and Neoplasiamentioning

confidence: 99%

“…Many different strategies have been used in an attempt to modify or suppress HuR's action in cancer [27], including inhibiting its cytoplasmic translocation, decreasing its expression via siRNAs or inhibiting its binding to target mRNAs. On top of that, intense research has been performed to obtain data regarding the synergistic use of HuR inhibition with chemotherapeutic and a variety of other agents [53][54][55][56][57] (Figure 2, Table 1).…”

Section: Agents Interacting With Hur Expression and How Hur's Inhibition Could Affect Tumor Progressionmentioning

confidence: 99%

Divulging the Critical Role of HuR in Pancreatic Cancer as a Therapeutic Target and a Means to Overcome Chemoresistance

Goutas

Theocharis

2021

Cancers

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Pancreatic cancer is set to become the most lethal and common type of cancer worldwide. This is partly attributed to the mutational burden that affects core signaling pathways and the crosstalk of tumor cells with their surrounding microenvironment, but it is also due to modern eating habits. Hyperadiposity along with the constant rise in metabolic syndrome’s incidence contribute to a state of metaflammation that impacts immune cells and causes them to shift towards an immunosuppressive phenotype that, ultimately, allows tumor cells to evade immune control. Unfortunately, among the conventional therapeutic modalities and the novel therapeutic agents introduced, pancreatic cancer still holds one of the lowest response rates to therapy. Human antigen R (HuR), an RNA binding protein (RBP), has been repeatedly found to be implicated in pancreatic carcinogenesis and chemotherapy resistance through the posttranscriptional binding and regulation of mRNA target genes. Additionally, its overexpression has been linked to adverse clinical outcomes, in terms of tumor grade, stage, lymph node status and metastasis. These properties suggest the prospective role that HuR’s therapeutic targeting can play in facilitating pancreatic neoplasia and could provide the means to overcome chemoresistance.

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HuR as Therapeutic Target in Cancer: What the Future Holds

Cited by 20 publications

References 57 publications

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

MicroRNAs, Tristetraprolin Family Members and HuR: A Complex Interplay Controlling Cancer-Related Processes

Divulging the Critical Role of HuR in Pancreatic Cancer as a Therapeutic Target and a Means to Overcome Chemoresistance

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