LINC01134 Directly Binds and Regulates SLC1A5 Stability to Promotes Colorectal Cancer Progression.

J Cancer

Department of cardiovascular medicine, Shanghai Punan Hospital, 219 Linyi Road, Pudong New Area, 200125, Shanghai, China.

Published: October 2024

AI Article Synopsis

  • Colorectal cancer (CRC) is a serious cancer with bad outcomes, and long noncoding RNAs (lncRNAs) like LINC01134 are important in its progression.
  • This study found that high levels of LINC01134 in CRC tissues are linked to advanced stages of the disease and worse prognosis.
  • The research shows that LINC01134 promotes CRC cell growth by stabilizing the mRNA of another gene, SLC1A5, indicating that targeting LINC01134 might be a potential treatment strategy for CRC.

Article Abstract

Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. Long noncoding RNAs (lncRNAs) have recently gained attention for their pivotal role in regulating cancer progression, including CRC. This study aimed to investigate the biological mechanisms underlying the participation of long intergenic non-protein coding RNA 1134 (LINC01134) in the progression of CRC. Quantitative Real-time-PCR (RT-qPCR) and western blot were applied to assess the expression levels of mRNA and protein. Functional experiments (CCK8 assay, colon formation assay, EdU assay and flow cytometry) were applied to assess cell viability and apoptosis. RNA-RNA interaction assays, subcellular fractionation analysis and dual luciferase reporter assays were employed to explore molecular interactions between LINC01134 and solute carrier family 1 member 5 (SLC1A5). The mRNA stability was analyzed using actinomycin D (ActD). We found that LINC01134 expression was highly expressed in CRC tissues and positively correlated with advanced clinical stages and unfavorable prognosis, which is consistent with findings from CRC cell lines. Functional experiments showed that suppressing LINC01134 restrained the proliferation of CRC both and and induced apoptosis of CRC cells. Gene co-expression analysis revealed a positive relationship between LINC01134 and SLC1A5, which was also upregulated and associated with unfavorable prognosis in CRC. Further analysis of RNA interactions and mRNA stability revealed that LINC01134 directly binds to SLC1A5 mRNA, enhancing its stability. Remarkably, silencing SLC1A5 expression partially counteracted the promotion of CRC cell proliferation by LINC01134 overexpression and alleviated its inhibition of apoptosis. Our findings indicated that LINC01134 functioned as an oncogene in CRC by binding directly to SLC1A5 mRNA and increasing its stability. Therefore, targeting LINC01134 could be a potential therapeutic target for treating CRC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493009PMC
http://dx.doi.org/10.7150/jca.100147DOI Listing

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