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Objective <p>Carbonic anhydrase IX (CAIX) expression in tumors is induced in response to hypoxia leading to loss of cellular adhesion and tumor cell progression. This study was pursued to identify a specific long non-coding RNA for targeting CAIX in colorectal cancer (CRC) and its consequence on cancer cell features.</p> Methods <p>Through bioinformatics, CAIX gene was selected to identify non-coding RNAs associated with CAIX. Then the expression of CAIX-specific mRNA and the lncRNA were compared in human CRC biopsies (<i>n</i> = 50) and their normal adjacent biopsies using quantitative real-time polymerase chain reaction (qRT-PCR). CAIX expression was evaluated in HCT116 cell line after blocking the lncRNA by Antisense Oligonucleotide (ASO). Expression of the target genes and cellular behavior; cell proliferation rate, apoptosis, cell migration and invasion were examined.</p> Results <p>LncRNA-TRPM2-AS and CAIX expressions were markedly higher (&gt; 8 fold) in CRC malignant tissues compared to normal adjacent tissues. This increase was more in stage II/III tumors. Blocking lncRNA TRPM2-AS expression in HCT116 cell line resulted in ~ 50% suppression in CAIX expression, as well as inhibition in cell proliferation and migration. Accordingly, the rate of cell death was enhanced in the cancer cells.</p> Conclusions <p>LncRNATRPM2-AS can efficiently control hypoxia in CRC cells by targeting CAIX. This is evidenced by showing the overexpression of lncRNA and CAIX in CRC tumors as well as the suppressive effects of lncRNA TRPM2-AS on CAIX expression in the HCT116 cell line. This data suggests CAIX down-regulation by lncRNA TRPM2, as a therapeutic target to suppress hypoxia-related progression and drug resistance in tumor cells.</p>

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Regulation of carbonic anhydrase IX gene expression through the LncRNA TRPM2-AS is associated with tumor progression in colorectal tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月21日

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  • Marziye Emamian,
  • Samane Sharif,
  • Baratali Mashkani,
  • Mohammadreza Abbaszadegan,
  • Abdolamir Allameh

摘要

Objective

Carbonic anhydrase IX (CAIX) expression in tumors is induced in response to hypoxia leading to loss of cellular adhesion and tumor cell progression. This study was pursued to identify a specific long non-coding RNA for targeting CAIX in colorectal cancer (CRC) and its consequence on cancer cell features.

Methods

Through bioinformatics, CAIX gene was selected to identify non-coding RNAs associated with CAIX. Then the expression of CAIX-specific mRNA and the lncRNA were compared in human CRC biopsies (n = 50) and their normal adjacent biopsies using quantitative real-time polymerase chain reaction (qRT-PCR). CAIX expression was evaluated in HCT116 cell line after blocking the lncRNA by Antisense Oligonucleotide (ASO). Expression of the target genes and cellular behavior; cell proliferation rate, apoptosis, cell migration and invasion were examined.

Results

LncRNA-TRPM2-AS and CAIX expressions were markedly higher (> 8 fold) in CRC malignant tissues compared to normal adjacent tissues. This increase was more in stage II/III tumors. Blocking lncRNA TRPM2-AS expression in HCT116 cell line resulted in ~ 50% suppression in CAIX expression, as well as inhibition in cell proliferation and migration. Accordingly, the rate of cell death was enhanced in the cancer cells.

Conclusions

LncRNATRPM2-AS can efficiently control hypoxia in CRC cells by targeting CAIX. This is evidenced by showing the overexpression of lncRNA and CAIX in CRC tumors as well as the suppressive effects of lncRNA TRPM2-AS on CAIX expression in the HCT116 cell line. This data suggests CAIX down-regulation by lncRNA TRPM2, as a therapeutic target to suppress hypoxia-related progression and drug resistance in tumor cells.