MicroRNA-93 mediates cabergoline resistance by targeting ATG7 in prolactinoma

Wu, Zerui; Cai, Lin; Lu, Jianglong; Wang, Cheng De; Guan, Jiaqing; Chen, Xianbin; Wu, Jinsen; Zheng, Wenjie; Wu, Zhe Bao; Li, Qun; Su, Zhipeng

doi:10.1530/joe-18-0203

Cited by 22 publications

(18 citation statements)

References 36 publications

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“…ATG genes are also involved in mediating resistance to chemotherapies, and these can be the potential targets for future treatment options. One known mechanism involves ATG‐7 gene, responsible for cabergoline resistance in prolactinomas and it gets mediated by miR‐93, which downregulates autophagy by targeting ATG‐7 140 . ATG7 overexpression is also involved in bladder cancer growth and tumorigenesis via FOXO1/p27 141 .…”

Section: Regulatory Factors With Mechanismsmentioning

confidence: 99%

Role and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance

Usman

Razzaq

Akbar

et al. 2020

Asia-Pac J Clncl Oncology

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A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy‐induced tumorigenesis and drug resistance including Beclin‐1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF‐2, MEG3, LAPTM4B, mTOR, BRAF and c‐MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

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Section: Regulatory Factors With Mechanismsmentioning

confidence: 99%

Role and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance

Usman

Razzaq

Akbar

et al. 2020

Asia-Pac J Clncl Oncology

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“…Recent evidence has revealed that several miRNAs are involved, among other functions, in regulating drug resistance in multiple tumors, including pituitary tumors (95)(96)(97)(98)(99).…”

Section: The Role Of B-arrestinsmentioning

confidence: 99%

“…miR-93, miR-17, miR-22, miR-126, miR-142-3p, miR-144, miR-486-5p, miR-451 and miR-92a were up-regulated while miR-30a, miR-382, miR-136 have been found down-regulated in BRC-resistant prolactinomas compared to BRC-sensitive prolactinomas ( 97 ). Interestingly, the knockdown of endogenous miR-93-5p by the miRNA inhibitor antagomir transfection in MMQ cells has been shown to significantly increase the sensitivity to BRC and CAB treatment inducing cell proliferation inhibition, whereas overexpression of miR-93-5p with the miRNA mimic agomir transfection blunted the anti-secretive effect of BRC on PRL release ( 95 ) and suppressed the cytotoxic effect of CAB in MMQ and GH3 cells ( 97 , 99 ). The DAs resistance induced by the overexpression of miR-93-5p in MMQ and GH3 cell lines involves the down-regulation of the protein p21, a key member of cyclin kinase inhibitors known to be implicated in the inhibition of cell-cycle progression, as demonstrated in MMQ cell line ( 97 ), and the down-regulation of the protein Autophagy Related 7 (ATG7), an essential regulator of autophagy, decreasing the autophagic cell death induced by CAB in MMQ and GH3 cell lines and rat pituitary tumors ( 99 ).…”

Section: Drs Expression In Pituitary Tumors: Mechanisms Of Resistancementioning

confidence: 99%

Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms

et al. 2022

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Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.

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“…Wu et al [ 51 ] studied the involvement of miR-93 in resistant prolactinomas to dopamine agonists (DAs), such as cabergoline (CAB). They found that, in MMQ and GH3 cells, this miRNA was able to target autophagy-related gene 7 (ATG7) protein, leading to cell autophagy inhibition and CAB resistance, while the downregulation of miR-93 had the opposite effects, with subsequent increase in the apoptosis process.…”

Section: Mirnas In Secreting Pasmentioning

confidence: 99%

MicroRNAs as Potential Biomarkers in Pituitary Adenomas

Donati

Aurilia

Palmini

et al. 2021

ncRNA

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Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs.

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MicroRNA-93 mediates cabergoline resistance by targeting ATG7 in prolactinoma

Cited by 22 publications

References 36 publications

Role and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance

Role and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance

Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms

MicroRNAs as Potential Biomarkers in Pituitary Adenomas

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