Deep sequencing-based microRNA expression signatures in head and neck squamous cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs

Abstract

We adopted into RNA-sequencing technologies to construct the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Our signature revealed that a total of 160 miRNAs (44 upregulated and 116 downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150-5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR-150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR-150-3p predicted significantly shorter overall survival in patients with HNSCC (P = 0.0091 and P = 0.0386) by Kaplan–Meier survival curves analyses. We identified that integrin α3 (ITGA3), integrin α6 (ITGA6), and tenascin C (TNC) were coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026, respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification of antitumor miR-150-mediated RNA networks may provide novel insights into pathogenesis of HNSCC.

Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance

“…Passenger strands of miRNAs are also thought to undergo degradation, becoming nonfunctional . Contrary to this point of view, our miRNA signatures showed that some miRNA passenger strands were aberrantly expressed in several cancer tissues . Our previous studies revealed that miR‐145‐3p (the passenger strand of the miR‐145 duplex) was significantly reduced in clinical specimens of prostate cancer as well as head and neck squamous cell carcinoma.…”

Molecular pathogenesis of renal cell carcinoma: Impact of the anti‐tumor miR‐29 family on gene regulation

“…Based on our original miRNA expression signatures, including that for RCC, we have identified RNA networks that are controlled by anti‐tumor miRNAs in several cancers . Downregulation of the miR‐29 family ( miR‐29a , miR‐29b and miR‐29c ) was frequently observed in many types of cancers .…”

Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis

“…The procedure for PCR quantification was described previously [19][20][21][22][23]. TaqMan probes and primers for HMGB3 ((P/N: Hs00801334_m1; Applied Biosystems) were assayon-demand gene expression products.…”

“…Anti-glyceraldehyde 3-phosphate dehydrogenase (GAPDH) antibodies (1:10,000 dilution; ab8245; Abcam, Cambridge, UK) were used as an internal control. The procedures were described in our previous studies [19][20][21][22][23].…”

“…The starting point of our strategy of miRNA studies is to identify aberrantly expressed miRNAs based on miRNA expression signatures [17][18][19][20][21]. Analyses of our miRNA signatures of PCa and CRPC have revealed that miR-205-5p is downregulated in cancer tissues [16][17][18]22].…”