miR-1238 inhibits cell proliferation by targeting LHX2 in non-small cell lung cancer

Abstract

In human cancers, dysregulated expression of LIM-homeobox gene 2 (LHX2) and downregulation of miR-1238 has been reported separately. However, the relationship between them remains unclear. We investigated the functional contribution of miR-1238 to the regulation of LHX2 in non-small cell lung cancer (NSCLC). Here, computational algorithms predicted that the 3′-untranslated region (3′-UTR) of LHX2 is a target of miR-1238. Luciferase assays validated that miR-1238 directly bound to 3′-UTR of LHX2. qRT-PCR and western blot analyses further confirmed that overexpression of miR-1238 mimic in NSCLC A549 and LTEP-α-2 cells inhibited endogenous expression of LHX2 mRNA and protein. Moreover, ectopic expression of miR-1238 in NSCLC A549 and LTEP-α-2 cells suppressed cellular viability and proliferation. siRNA-induced knockdown of LHX2 copied the phenotype of miR-1238 overexpression in NSCLC A549 and LTEP-α-2 cells and LHX2 knockdown inhibited cell cycle. In addition, miR-1238 expression was frequently decreased in human NSCLC tissues and reversely correlated with LHX2 expression, which was increased in NSCLC tissues. Collectively, our findings demonstrate that miR-1238 inhibit the proliferation of NSCLC cells at least partly via repression of LHX2, shedding light on the mechanistic interaction of miR-1238 and LHX2 in NSCLC carcinogenesis. Furthermore, our data suggest that expression of miR-1238 could be a promising therapeutic strategy for NSCLC treatment.

Repression of Smad4 by miR-205 moderates TGF-β-induced epithelial-mesenchymal transition in A549 cell lines

“…Approximately 30% of messenger RNAs are regulated by miRNAs (19). Thus, miRNAs represent a group of important players in diverse biological and pathological processes, including tumor cell proliferation, differentiation, and survival (20)(21)(22)(23). Recently a study showed that the expression of microRNAs appear to be tissue or tumor type-specific (24), and there is accumulating evidence showing that it could be a candidate biomarker for clinical diagnosis, including identification of cancer type or tumor subtype (25,26).…”

HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis

“…Beside its role as tumor-suppressor [19], miR-16 was recently shown to affect NK function by repressing IFNγ expression [20], and to promote M1 pro-inflammatory type macrophage polarization, affecting T cell activation [21]. No data are instead available on miR-1238 potential functions in immunity, as it was so far recognized only as a tumor-suppressor factor [22]. However, it was identified as a marker of AITD [23], together with miR-143_1, and the strong increase observed in both thyroid and lymphoid HHV-6A infected cells suggest a potential role of miR-1238 in the modulation of immune response, and deserves further studies.…”

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor

“…To date, the powerful gene regulators microRNAs have been implicated in many pathophysiological processes, including cell development, proliferation, apoptosis, and carcinogenesis [20,38,39]. Accumulating evidence has shown that many miRNAs are also critically involved in the pathogenesis of human tissue fibrosis of in several organs [40].…”

“…Additionally, the reason for the TGFBR2 alterations observed in SSc also remains unclear, especially concerning epigenetics. MiRNAs are endogenous, single-stranded, evolutionarily conserved noncoding RNAs about 24 nucleotides in length that act as crucial posttranscriptional regulators through binding to the 3ʹ-untranslated regions (3′-UTRs) of their target genes [20]. Currently, the specific signatures of SSc have been detected by examination of miRNA profiles in serum, skin tissues, and fibroblasts [21][22][23][24].…”