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Myosin Heavy Chain-Associated RNA Transcripts Promotes Gastric Cancer Progression Through the miR-4529-5p/ROCK2 Axis

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Abstract

Background and Aim

Characterization of genetic aberrations provides novel strategies for diagnosis and treatment of gastric cancer. Accumulating evidence has shown the involvement of long non-coding RNA (lncRNA) in the pathology of gastric cancer, especially in proliferation and metastasis. The aim of this study was to delineate the role of myosin heavy chain-associated RNA transcripts (MHRT), a heart-specific lncRNA, in gastric cancer and to understand the correlation between MHRT, miR-4529-5p, and ROCK2.

Methods

To study expression level of MHRT, clinical gastric cancer samples, gastric cancer cell lines, adjacent normal tissues, and gastric epithelial cell lines were used. Additionally, apoptosis, proliferation, and invasion of gastric cancer cells were studied with or without downregulation of MHRT and miR-4529-5p.

Results

We identified that MHRT was ectopically expressed in gastric cancer tissues and cell lines. Interestingly, similar to the anti-apoptotic role of MHRT in cardiomyocytes, our data illustrated that MHRT inhibits apoptosis of gastric cancer cells. Moreover, we found that MHRT promotes proliferation and invasion of gastric cancer cells in vitro. Importantly, our data revealed that MHRT regulates the expression of miR-4529-5p via direct binding. Additionally, functional experiments illustrated that miR-4529-5p is particularly responsible for MHRT-mediated regulation of apoptosis. Besides, ROCK2 was identified as a downstream target of miR-4529-5p. Additionally, upregulated MHRT promotes the expression of ROCK2 by inhibiting miR-4529-5p.

Conclusion

Our data illustrated a MHRT/miR-4529-5p/ROCK2 regulatory axis that contributes to the tumorigenesis of gastric cancer and provided potential therapeutic targets for precise gastric cancer treatment.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The present study was supported by the Collaborative Innovation Project of Shaanxi Province (No. 2015XT-53), Social Development Project of Shaanxi Province (No. 2018SF-188).

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Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, No 157 Xinwu Road, Xi’an, 710004, China

    Xiaoli Sun, Xinwu Zhang, Shuo Chen, Meng Fan, Shuangyu Ma & Hongjun Zhai

Authors
  1. Xiaoli Sun
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  2. Xinwu Zhang
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  3. Shuo Chen
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  4. Meng Fan
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  5. Shuangyu Ma
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  6. Hongjun Zhai
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Contributions

XS, XZ, and HZ conceived and designed the experiments; SC and MF performed the experiments; XS contributed reagents/materials/analysis tools. HZ and XS wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hongjun Zhai.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of The Second Affiliated Hospital of Xi’an Jiaotong University.

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10620_2019_5708_MOESM1_ESM.tif

Figure S1 (A)Quantification of migrated SGC-7901 and BGC-823 cells with basal MHRT or downregulated MHRT.;(B)Quantification of invaded SGC-7901 and BGC-823 cells with basal MHRT or downregulated MHRT. (TIFF 2908 kb)

Figure S2 Quantification of invasioned SGC-7901 and BGC-823 cells with indicated treatment. (TIFF 4622 kb)

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Sun, X., Zhang, X., Chen, S. et al. Myosin Heavy Chain-Associated RNA Transcripts Promotes Gastric Cancer Progression Through the miR-4529-5p/ROCK2 Axis. Dig Dis Sci 64, 3539–3548 (2019). https://doi.org/10.1007/s10620-019-05708-1

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  • DOI: https://doi.org/10.1007/s10620-019-05708-1

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