The miR-1224-5p/TNS4/EGFR axis inhibits tumour progression in oesophageal squamous cell carcinoma

Abstract

Oesophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy. Although many molecular alterations have been observed in ESCC, the mechanisms underlying the development and progression of this disease remain unclear. In the present study, miR-1224-5p was identified to be downregulated in ESCC tissues compared to normal tissues, and its low expression was correlated with shorter survival time in patients. In vitro experiments showed that miR-1224-5p inhibited the proliferation, colony formation, migration and invasion of ESCC cells. Mechanistic investigation revealed that miR-1224-5p directly targeted TNS4 and inhibited its expression, which led to the inactivation of EGFR-EFNA1/EPHA2-VEGFA (vascular endothelial growth factor A) signalling. Experiments in vivo confirmed the suppressive effect of miR-1224-5p on oesophageal cancer cells. By immunohistochemistry analysis of ESCC specimens, we found that TNS4 expression was positively correlated with that of VEGFA, and was significantly associated with lymph node metastasis and shorter survival time in patients. Together, our data suggest that miR-1224-5p downregulation is a frequent alteration in ESCC that promotes cell proliferation, migration, invasion and tumour growth by activating the EGFR-EFNA1/EPHA2-VEGFA signalling pathway via inhibition of TNS4 expression. Decreased miR-1224-5p and elevated TNS4 are unfavourable prognostic factors for ESCC patients.

miR-17-5p and miR-4443 Promote Esophageal Squamous Cell Carcinoma Development by Targeting TIMP2

“…For example, miR-148a might play its oncogenic role by targeting AVR1 in ESCC ( 16 ). miR-1224-5p inhibits tumor progression by targeting the TNS4/EGFR axis ( 17 ). There are also several types of research confirmed the oncogenetic roles of miR-17-5p.…”

RNA-Seq profiling of circular RNAs in human colorectal cancer 5-fluorouracil resistance and potential biomarkers

“…Accumulating evidence has suggested that TNS4 may be involved in the pathogenesis of cancers by interacting with miRNAs. For instance, miR-1224-5p inhibits TNS4, subsequently affecting the progression of oesophageal squamous cell carcinoma[ 36 ]. According to a recent report, TNS4 was identified as a key effector of cetuximab and a regulator of the oncogenic activity of KRAS mutant CRC[ 37 ].…”

Exosomal-mediated transfer of APCDD1L-AS1 induces 5-fluorouracil resistance in oral squamous cell carcinoma via miR-1224-5p/nuclear receptor binding SET domain protein 2 (NSD2) axis

“…MiR-1224-5p played an anti-cancer role in various cancers, such as rectal cancer [ 41 ], pancreatic cancer [ 42 ], ovarian cancer [ 43 ], and glioma [ 44 ]. In addition, a report from Shi et al also elucidated that miR-1224-5p could impair the development of esophageal squamous cell carcinoma, which is another HNSC subtype [ 45 ]. In the current study, miR-1224-5p was targeted and negatively regulated by APCDD1L-AS1 in OSCC cells resistant to 5-FU.…”