miR-33a is a tumor suppressor microRNA that is decreased in prostate cancer

Abstract

Prostate cancer is one of the most frequently diagnosed neoplasms among men worldwide. MicroRNAs (miRNAs) are involved in numerous important cellular processes including proliferation, differentiation and apoptosis. They have been found to be aberrantly expressed in many types of human cancers. They can act as either tumor suppressors or oncogenes, and changes in their levels are associated with tumor initiation, progression and metastasis. miR-33a is an intronic miRNA embedded within SREBF2 that has been reported to have tumor suppressive properties in some cancers but has not been examined in prostate cancer. SREBF2 increases cholesterol and lipid levels both directly and via miR-33a action. The levels of SREBF2 and miR-33a are correlated in normal tissues by co-transcription from the same gene locus. Paradoxically, SREBF2 has been reported to be increased in prostate cancer, which would be predicted to increase miR-33a levels potentially leading to tumor suppression. We show here that miR-33a has tumor suppressive activities and is decreased in prostate cancer. The decreased miR-33a increases mRNA for the PIM1 oncogene and multiple genes in the lipid β-oxidation pathway. Levels of miR-33a are not correlated with SREBF2 levels, implying posttranscriptional regulation of its expression in prostate cancer.

Antiproliferative potential of miR‐33a in laryngeal cancer Hep‐2 cells via targeting PIM1

“…The MiR‐33a is an intronic microRNA that resides within the 16 th intron of the SREBF2 gene with critical roles associated with regulation of lipid and cholesterol metabolism . It has also been reported as an important tumor suppressor in distinct tumor types through deregulating its targets' expressions . Our investigation of a recent dataset, in which microRNAs in CD133‐positive and CD133‐negative cells were profiled, demonstrated that miR‐33a expression in CD133‐positive cells, which were demonstrated to possess cancer stemlike features, is significantly lower compared to corresponding CD133‐negative cells, indicating a tumor suppressor function for miR‐33a.…”

“…14 It has also been reported as an important tumor suppressor in distinct tumor types through deregulating its targets' expressions. 13,[15][16][17][18][19][20][21] Our investigation of a recent dataset, in which microRNAs in CD133-positive and CD133-negative cells 24 were profiled, demonstrated that miR-33a expression in CD133-positive cells, which were demonstrated to possess cancer stemlike features, 34 is significantly lower compared to corresponding CD133-negative cells, indicating a tumor suppressor function for miR-33a. Cancer stem cells, resembling normal stem cells in their biologic features, are thought to be an important component of tumors, leading to cancer initiation, development, recurrence, invasion, metastases, and therapy resistance.…”

“…MicroRNA-33a (miR-33a) is a highly conserved micro-RNA with roles in regulation of lipid and cholesterol metabolisms 14 that exerts tumor suppressive potential in distinct cancers 13,[15][16][17][18][19][20][21] through targeting multiple oncogenes; 13,19,22,23 however, miR-33a and its targets have not been examined in laryngeal cancer.…”

Identification of PIM1 substrates reveals a role for NDRG1 in prostate cancer cellular migration and invasion

“…As such, PIM1 is regulated primarily by transcription, including induction by cytokines through the JAK/STAT pathway 5 and by hypoxia 6 . PIM1 protein levels are also regulated translationally via its 5' UTR 7 and by the microRNA miR-33a 8 . PIM1 has been implicated as an oncogene in both hematological malignancies, such as large B cell lymphoma 9 , and cancers of epithelial origins, such as breast and prostate cancer [10][11][12][13] .…”

Multi-view Co-training for microRNA Prediction

“…Ev idence suggests that approximately 60-90% of mRNA have the potential to be targeted by miRNA [8]. Recent studies have also suggested that miRNA may act as tumor suppressors in different cancers such as liver [9], colon [10], prostate [11] and bladder cancers [12].…”