Cancer Medicine (Nov 2020)

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

  • Mingming Zhu,
  • Yang Luo,
  • Antao Xu,
  • Xitao Xu,
  • Ming Zhong,
  • Zhihua Ran

DOI
https://doi.org/10.1002/cam4.3473
Journal volume & issue
Vol. 9, no. 22
pp. 8639 – 8649

Abstract

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Abstract 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.