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  • Long noncoding RNA TCONS_00026334 is involved in suppressing the progression of colorectal cancer by regulating miR-548n/TP53INP1 signaling pathway.

Long noncoding RNA TCONS_00026334 is involved in suppressing the progression of colorectal cancer by regulating miR-548n/TP53INP1 signaling pathway.

Cancer medicine (2020-09-29)
Mingming Zhu, Yang Luo, Antao Xu, Xitao Xu, Ming Zhong, Zhihua Ran
RÉSUMÉ

Recently, long noncoding RNAs (lncRNAs) were recognized as significant therapeutic targets in tumors. Our previous microarray analysis showed that lncRNA TCONS_000026334 expression was reduced in metastatic colorectal cancer (CRC) tissues. The objective of this study was to research the biological functions of TCONS_000026334 and the potential mechanism during the development of CRC. TCONS_00026334 transcription levels were detected in CRC tissues from 86 patients and different CRC cell lines. The clinical prognosis factors related to TCONS_00026334 expression were then analyzed. TCONS_000026334 was overexpressed from plasmid pcDNA3.1-TCONS_ 000026334 or knocked down using a small interfering RNA (siRNA). Furthermore, bioinformatics approach and luciferase reporter gene assays were utilized to search for candidate miRNAs of TCONS_00026334 and identify the downstream target genes. The results indicated that TCONS_00026334 expression in 86 CRC tissues was markedly lower than that in non-cancerous tissues. The aberrant expression of TCONS_00026334 correlated negatively with larger tumor size, distant metastasis, serological carcinoembryonic antigen level, and unfavorable survival of patients with CRC. TCONS_00026334 overexpression could inhibit the aggressive phenotypes of CRC in vitro and in vivo. Conversely, TCONS_00026334 silencing accelerated CRC cell proliferation and invasion. We then verified that TCONS_00026334 upregulated the expression level of TP53INP1, a target gene of miR-548n, via direct binding to miR-548n as a competing endogenous RNA. Taken together, our study showed that TCONS_00026334 acts as an anti-tumor and anti-metastatic gene by regulating the miR548n/TP53INP1 axis in the development of CRC.