MicroRNA‑216a‑5p suppresses esophageal squamous cell carcinoma progression by targeting KIAA0101

Abstract

The KIAA0101 protein (also referred to as NS5ATP9 or Paf15) is overexpressed in esophageal squamous cell carcinoma (ESCC) and is associated with disease progression and poor patient survival, but how KIAA0101 expression is regulated remains unknown. The relationship between tumor miR-216a-5p expression and prognosis in patients with ESCC was revealed by survival analyses. Quantitative reverse-transcriptase PCR and western blot analysis were used to evaluate miR-216a-5p and KIAA0101 expression in human ESCC tissues and cell lines. The targeting of KIAA0101 by miR-216a-5p was verified by dual-luciferase reporter assays. The EC9706 and TE1 cell lines were transfected with miR-216a-5p mimics and inhibitor, or KIAA0101-specific shRNA and KIAA0101-expressing plasmids, in order to evaluate the effect of manipulating miR-216a-5p and KIAA0101 expression on ESCC cell proliferation, cell cycle progression, migration, and invasion. miR-216a-5p was lowly expressed and inversely correlated with KIAA0101 protein expression in ESCC tissues and cell lines. Lower miR-216a-5p expression was associated with worse prognosis in patients with ESCC. miR-216a-5p negatively regulated KIAA0101 expression by directly targeting the 3'-untranslated region of the KIAA0101 mRNA. Overexpression of miR-216a-5p suppressed the proliferation, migration, and invasion of the ESCC cell lines, whereas inhibition of miR-216a-5p had the opposite effects. Meanwhile, KIAA0101 promoted ESCC migration and invasion, and its overexpression abolished the antitumor effects of miR-216a-5p mimics. As a tumor suppressor, miR-216a-5p targets KIAA0101 to inhibit the proliferation, migration, and invasion of ESCC. Therefore, the miR-216a-5p/KIAA0101 axis may be a potential target for ESCC treatment.

Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors

“…Studies in recent years have revealed that PCLAF is overexpressed in several types of GI tract tumors, including esophageal cancer[ 6 , 7 ], GC[ 8 - 10 ], and CRC[ 39 , 43 ]. Some studies have also shown a strong association between PCLAF and tumors in accessory organs of digestion, including PC[ 15 ] and liver cancer[ 12 - 14 , 44 - 46 ].…”

“…Knockdown of PCLAF increases cell numbers in the G1 phase by flow cytometry analysis, and downregulates the protein levels of cyclin A and B, indicating that PCLAF might control esophageal cancer cell viability via induction of cyclin A and B[ 7 ]. PCLAF also promoted cell migration and invasion in ESCC EC9706 and TE1 cell lines using the transwell assay[ 6 ]. Moreover, elevated PCLAF expression predicts a worse response to chemotherapy.…”

“…Furthermore, PCLAF is the target of miRNAs, including miR-1[ 88 ], miR-34a[ 51 ], miR-139-3p[ 31 ], miR-183[ 66 , 89 ], miR-197-5p[ 30 ], miR-216a-5p[ 6 ], and miR-429[ 32 ]. A study of prostate cancer showed that PCLAF was negatively correlated with miR-1 and was identified as a crucial miR1 target gene[ 88 ].…”

“…MiR-197-5p and miR-429, as tumor suppressors, suppress cell migration, invasion, and anchorage-independent growth of fibrosarcoma cells possibly by targeting PCLAF during sarcoma genesis[ 30 , 32 ], suggesting that PCLAF is also an underlying target of miR-197-5p and miR-429. A recent study has also shown that miR216a5p suppresses the proliferation, migration, and invasion of ESCC cell lines (EC9706 and TE1) and negatively regulates PCLAF expression by directly targeting the 3’-UTR of PCLAF mRNA[ 6 ]. In the above studies, PCLAF serves as a therapeutic target in different tumors.…”

“…Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), a 15-KD protein-containing PCNA-binding motif [PIP box, Qxx(L/I/M)xx(F/Y)(F/Y)], is a potential molecular target of GI cancers. PCLAF is associated with several types of GI tract cancers, such as esophageal cancer[ 6 , 7 ], gastric cancer (GC)[ 8 - 10 ], colorectal cancer (CRC)[ 11 ], and accessory organs of digestion cancers, including liver cancer[ 12 - 14 ], and pancreatic cancer (PC)[ 15 ].…”