Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy that exhibits distinct geographical and ethnic prevalence [
1,
2]. Although the contemporary therapeutic approach of radio-/chemotherapy provides excellent results for patients with early-stage disease, it is far from satisfactory for those with disease remission and distant metastasis, which are highly fatal. [
3]. Identification of promising therapeutic targets for patients with advanced disease is urgently needed. Despite continuous efforts in NPC research, our understanding of the mechanisms that regulate tumor progression is limited. In the past decade, the cancer stem-like cell (CSC) subpopulation was proposed to play a critical role in local relapse and metastasis in human cancers [
4,
5]. These CSCs have the ability to self-renew, differentiate, and sustain propagation and are commonly unresponsive to conventional treatments [
6]. Targeting of the CSC subpopulation and suppression of the properties of CSCs are believed to enhance the efficacy of radiotherapy and chemoradiotherapy [
6]. In our earlier study, we identified and characterized an NPC CSC subpopulation that is suggested to be a potential culprit for the metastasis of this EBV-associated malignancy [
7,
8]. Using microarray analysis, we revealed a number of differentially expressed genes in transcription regulation (e.g.,
FOXN4 and
GLI1), immune response (
CCR7), and transmembrane transport (e.g.,
ABCC3 and
ABCC11) in the spheroids [
7]. Aside from these cellular genes, microRNA (miRNA) microarray analysis also identified a number of differentially expressed miRNAs in the NPC CSCs. MiRNAs are small (approximately 22 nucleotides) non-coding RNAs that regulate gene expression [
9]. Since the elucidation of the roles of miRNAs in developmental processes, studies have focused on their involvement in cancer [
9,
10]. Interestingly, certain miRNA clusters, such as the
miR-183-96-182 cluster, play crucial roles in regulating stemness properties and drug resistance in cancer cells [
11]. Wellner et al. showed that overexpression of
miR-183, miR-203, and
miR-200c decreases the sphere-forming capacity of pancreatic cancer cells [
12]. It has been suggested that repression of these stemness-inhibiting miRNAs maintains the stem cell phenotype and is implicated in cancer progression [
13‐
16]. Among the differentially expressed miRNAs identified in NPC spheroids, several stemness-inhibiting miRNAs including
miR-96 and
miR-183 were downregulated in the NPC CSCs. In the present study, we confirmed that
miR-96 and
miR-183 have the highest fold changes. We then performed a functional study to elucidate whether
miR-96 and
miR-183 are NPC tumor suppressors that repress CSC properties. Our findings demonstrated that the ectopic expression of
miR-96 and
miR-183 suppressed the colony- and sphere-forming ability of NPC cells in vitro. However, only NPC cells stably expressing
miR-183 could inhibit tumor formation in vivo in a nude mice model.
MiR-183 has a potent effect on the suppression of CSC properties in vitro and in vivo and may play a contributory role in NPC tumorigenesis.