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Ali A. Alshamrani د. علي بن عبدالله آل هشبول الشمراني

Assistant Professor

أستاذ علم الأدوية والسموم المساعد | عضو هيئة تدريس

كلية الصيدلة
Building 23, College of Pharmacy, 1st floor, Office 1A 6
المنشورات
مقال فى مجلة
2018

miR-122-5p Expression and Secretion in Melanoma Cells is Amplified by the LPAR3 SH3 Binding Domain to Regulate Wnt1

Alshamrani, Ali A. . 2018

miR-122-5p PGC-1a LPAR3 WNT1 beta-catenin

The lysophosphatidic acid receptor-3 (LPAR3) is a G protein–coupled receptor that mediates viability among malignant cells and aggressiveness among certain tumors. The study's objective was to determine the interplay between LPAR3 and miRNAs to impact key cellular signaling pathways. Using SK-Mel-2 and SK-Mel-5 melanoma cells, wild-type and mutated receptors were stably expressed to explore molecular mechanisms. LPAR3 signaling induced miR-122-5p intracellularly and subsequently its inclusion into exosomes. This amplification resulted in less abundant Wnt1, maintenance of GSK3 inactivation and to a lesser extent, partial degradation of b-catenin. The surge in miR-122-5p and reduction in Wnt1 originated from signaling at the Src homology 3 (SH3) ligand–binding motif within the third intracellular loop of LPAR3, because mutant receptors did not increase miR-122-5p and had a weakened capacity to reduce Wnt1. In addition, a key mediator of melanoma survival signaling, the peroxisome proliferator-activated receptor gamma coactivator 1-a(PPARGC1A/PGC1), was involved in miR-122-5p transcrip- tion. In conclusion, this study highlights the powerful role miRNAs have in fine-tuning specific G protein–coupled receptor-mediated signaling events by altering the transcription of signaling transduction pathway components. This study also identifies that LPAR3 increases miR-122-5p expression, which occurs mechanistically through the SH3 domain and helps explain why miR-122-5p increases are detected in cancer patient serum.

Implications: LPAR3 is partially responsible for the production and secretion of miR-122-5p, found in the serum of a wide variety of patients with cancer.

رقم المجلد
17
رقم الانشاء
1
مجلة/صحيفة
Molecular Cancer Research
الصفحات
299-309
مزيد من المنشورات
publications

Various experimental and clinical studies strongly support a cigarette smoke-heart disease association and suggest possible mechanisms, unfortunately, the involvement of genetic modulations remain…

بواسطة Ali A. Alshamrani
2012
publications

The regulator of G protein signaling 10 (RGS10) protein is a GTPase activating protein that accelerates the hydrolysis of GTP and therefore canonically inactivates G proteins, ultimately…

بواسطة Ali A. Alshamrani
2015
publications

Autotaxin (ATX) is an enzyme discovered in the conditioned medium of cultured melanoma cells and identified as a protein that strongly stimulates motility.

بواسطة Ali A. Alshamrani
2015