Knockdown of circ_0001883 may inhibit epithelial‑mesenchymal transition in laryngeal squamous cell carcinoma via the miR‑125‑5p/PI3K/AKT axis

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with increasing incidence and poor prognosis. Circular RNAs (circRNAs) are known to modulate tumorigenesis and cancer development that may function through microRNAs (miRs). The aim of the present study was to investigate the functional roles of circ_0001883 in LSCC and the underlying molecular mechanism. The expression of circ_0001883 was upregulated and measured using reverse transcription-quantitative PCR (RT-qPCR) and RNase R. miR-125b-5p expression was downregulated in LSCC tissues and cells as determined using RT-qPCR. Subsequently, knockdown of circ_0001883 inhibited LSCC cell migration, invasion and epithelial-mesenchymal transition (EMT), which were tested by wound healing assays, Transwell assays and western blotting, respectively. Bioinformatics analysis predicted that circ_0001883 was a sponge of miR-125b-5p, which was verified using a dual-luciferase reporter assay. Knockdown of circ_0001883 played a functional role by sponging miR-125b-5p. Additionally, circ_0001883 and miR-125b-5p influenced phosphorylation of PI3K and AKT, detected via western blotting. In an in vivo study, knockdown of circ_0001883 reduced tumor volume and weight in mice, along with enhanced miR-125b-5p and E-cadherin expression levels, and decreased N-cadherin, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT ratios. In conclusion, knockdown of circ_0001883 inhibited cell migration, invasion and EMT of LSCC by sponging miR-125b-5p. This is hypothesized to be via the PI3K/AKT signaling pathway, which suggested that circ_0001883 has potential for LSCC therapy.

Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review

“…Of those, 166 were excluded for describing HNSCC cases without focus on the larynx ( n = 28), for being exclusively in vitro studies ( n = 39), for having a number of patients less than 10 or for using patient data from public databases ( n = 50), for not quantifying miRNAs in patient samples ( n = 43) and for other reasons, such as for not having statistically significant results or wrong miRNA sequence ( n = 6). Finally, the review was performed on a total of 177 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 …”

“…Other tissue miRNAs were reported by five or more articles, including miR-145-5p [ 32 , 42 , 59 , 92 , 99 , 130 , 131 , 153 , 167 ], miR-375-3p [ 28 , 140 , 145 , 149 , 159 , 171 , 178 , 188 , 196 ], miR-155-5p [ 26 , 28 , 59 , 84 , 106 , 128 , 169 ], miR-195-5p [ 75 , 107 , 111 , 114 , 115 , 146 , 197 ], miR-106b-3p [ 26 , 127 , 132 , 145 , 146 , 196 ], miR-21-3p [ 32 , 42 , 59 , 97 , 146 , 168 ], miR-125b-5p [ 32 , 43 , 82 , 101 , 117 , 130 ], miR-204-5p [ 32 , 49 , 65 , 82 ,…”

“…Only seven circulating miRNAs were reported by two or more studies, namely, miR-21-5p [ 57 , 143 , 174 ], miR-125b-5p [ 101 , 133 ], miR-126-3p [ 133 , 141 ], miR-223-3p [ 79 , 133 ], miR-27a-3p [ 133 , 191 ], miR-33a-5p [ 79 , 140 ] and miR-206 [ 43 , 133 ]. The main features of the selected miRNAs are shown in Table 2 .…”

Circular RNA circSLC7A11 contributes to progression and stemness of laryngeal squamous cell carcinoma via sponging miR-877-5p from LASP1

“…For instance, Fan et al illustrated that LSCC patients with high circ_0120175 expressions are interrelated to tumor stage, survival time, and circ_0120175 loss reduces LSCC growth [ 12 ]. Chen et al verified that circ_0001883 is abnormally overexpressed in LSCC, and circ_0001883 loss reduces LSCC growth via PI3K/AKT [ 13 ]. Additionally, circSLC7A11 (circBase ID: hsa_circ_0070975) originates exons 8, and 9 of SLC7A11 [ 14 ].…”

Hypoxanthine guanine phosphoribosyltransferase 1, a target of miR-125b-5p, promotes cell proliferation and invasion in head and neck squamous cell carcinoma

“…Aberrant expression of miRNAs regulates carcinogenesis by post-transcriptionally modulating the expression of its target genes, oncogenes, or tumor-suppressive genes [ 11 ]. Downregulation of miR-125b-5p suppresses the progression of HNSCC [ 13 , 14 ]. Interestingly, HPRT1 is a putative target of miR-125b-5p and negatively correlates with miR-125b-5p, suggesting that miR-125b-5p and HPRT1 may interact with each other to participate in HNSCC.…”