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Long noncoding RNA TCONS_00026334 is involved in suppressing the progression of colorectal cancer by regulating
Mingming Zhu1, Yang Luo2, Antao Xu1
1Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
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.
Insights
Long noncoding RNA TCONS_000026334 is downregulated in colorectal cancer (CRC). Its restoration inhibits CRC progression and metastasis by regulating the miR-548n/TP53INP1 pathway, suggesting therapeutic potential.
Area of Science:
- Molecular Oncology
- RNA Biology
- Cancer Therapeutics
Background:
- Long noncoding RNAs (lncRNAs) are emerging as critical regulators in tumorigenesis and potential therapeutic targets.
- Previous studies indicated reduced expression of lncRNA TCONS_000026334 in metastatic colorectal cancer (CRC) tissues.
Purpose of the Study:
- To investigate the functional roles of TCONS_000026334 in colorectal cancer development.
- To elucidate the underlying molecular mechanisms of TCONS_000026334 in CRC progression and metastasis.
Main Methods:
- Quantification of TCONS_000026334 expression in CRC tissues and cell lines.
- Analysis of clinical prognostic factors associated with TCONS_000026334 levels.
- In vitro and in vivo functional assays involving TCONS_000026334 overexpression and knockdown.
- Bioinformatics analysis, luciferase reporter assays to identify miRNA interactions and downstream targets.
Main Results:
- TCONS_000026334 expression was significantly lower in CRC tissues compared to non-cancerous tissues.
- Reduced TCONS_000026334 levels correlated with advanced tumor stage, distant metastasis, elevated CEA, and poor patient survival.
- Overexpression of TCONS_000026334 suppressed CRC cell proliferation and invasion, while knockdown accelerated these phenotypes.
- TCONS_000026334 functions as a competing endogenous RNA (ceRNA) by binding to miR-548n, thereby upregulating its target gene TP53INP1.
Conclusions:
- TCONS_000026334 acts as a tumor suppressor and anti-metastatic lncRNA in colorectal cancer.
- The miR-548n/TP53INP1 axis is a key regulatory pathway modulated by TCONS_000026334 in CRC.
- TCONS_000026334 holds promise as a potential biomarker and therapeutic agent for colorectal cancer.
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