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Low expression of LncRNA-CAF attributed to the high expression of HIF1A in esophageal squamous cell carcinoma and gastric cancer patients

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Abstract

Purpose

Cancer-associated fibroblasts (CAFs) are major components of tumor microenvironment that stimulate ESCC and GC progression. The LncRNA-CAF, FLJ22447, is located in the vicinity of HIF1A, while their association remains unclear. This study aims to assess the FLJ22447 expression in the ESCC and GC patients and evaluate its association with the HIF1A gene.

Methods

Fresh ESCC and GC tumor samples and their adjacent non-tumor tissues were collected from patients who underwent surgery in Imam Khomeini Hospital, Tehran, Iran. The expression of FLJ22447, HIF1A, and VEGF was evaluated using qRT-PCR test. The association of their expression with tumor clinicopathological features in ESCC patients was assessed. System biology tools were then applied for the possible biological subsequences of the FLJ22447.

Results

A significant reduction in FLJ22447 expression was observed in ESCC and GC tissues than adjacent non-tumor tissues, while, the expression of HIF1A and VEGF were increased. Low expression of FLJ22447 was significantly correlated with HIF1A (P = 2.4e–73, R = 0.63) and VEGF (P = 0.00019, R = 0.15) expression. A significant relationship was detected between the high expression of HIF1A and tumor stages (I–II) and it was related to the reduced survival of ESCC patients. Conversely, increased VEGF expression was linked to the advanced stages (III–IV) and metastasis in ESCC. The analysis of FLJ22447-interacted proteins showed that MYC, JUN, SMRCA4, PPARG, AR, FOS, and CEBPA are the hub genes. These proteins were implicated in the cancer related pathways. Among them, SPI1, E2F1, TCF7L2, and STAT1 were significantly expressed in esophageal and gastric cancers that were functionally involved in the proliferation, apoptosis, and angiogenesis pathways in cancer.

Conclusion

The results suggested that FLJ22447 may have a regulatory function on the HIF1A expression. We identified the FLJ22447-interacted proteins and their molecular function in cancer pathogenesis. Further research emphasis is to realize the association of FLJ22447 with its protein partners in progression of cancer. These may provide an insight into the FLJ22447 activity that could introduce it as a potential value in tumor gene therapy.

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Fig. 1
Fig. 2

adopted from GEPIA resources. Log2 (TPM + 1) was used for log-scale. ESCA esophageal carcinoma; TPM Transcripts per million

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Data availability

Data will be available while editor requested.

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Acknowledgements

We gratefully acknowledge all persons who helped us in this study in Molecular Genetic lab which was supported by Golestan University of Medical Sciences, Gorgan, Iran.

Funding

This research was supported in part by Golestan University of Medical sciences (Project Grant No. 960704177). The study sponsor had no role in the study design, collection, analysis and interpretation of the data or the writing of the report.

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Authors and Affiliations

  1. Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran

    Shabbou Bahramian, Zahra Roohinejad, Encieh Delshad & Fatemeh T. Shamsabadi

  2. Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Sahebi

  3. Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran

    Naeme Javid

  4. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran

    Abolfazl Amini & Fatemeh T. Shamsabadi

  5. Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

    Amirnader Emami Razavi

  6. Department of Medical Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran

    Mohammad Shafiee

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  1. Shabbou Bahramian
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  2. Reza Sahebi
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Corresponding authors

Correspondence to Mohammad Shafiee or Fatemeh T. Shamsabadi.

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This research was approved in Ethics Committee of by IR.GOUMS.REC.1397.006.

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Bahramian, S., Sahebi, R., Roohinejad, Z. et al. Low expression of LncRNA-CAF attributed to the high expression of HIF1A in esophageal squamous cell carcinoma and gastric cancer patients. Mol Biol Rep 49, 895–905 (2022). https://doi.org/10.1007/s11033-021-06882-0

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