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miR-140-3P Induces Chemotherapy Resistance in Esophageal Carcinoma by Targeting the NFYA-MDR1 Axis

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Abstract

Esophageal carcinoma (EC) is recognized as the 6th most frequent carcinoma in China, with esophageal squamous cell carcinoma (ESCC) being the predominant histologic type. Currently, chemotherapy is one among the most important therapy modalities for patients with ESCC. However, resistance to chemotherapeutic drugs leads to limited treatment options and poor prognosis. In our study, the analysis of small RNA sequencing and digital gene expression (DGE) profiling was done to recognize the microRNAs (miRNAs) and key genes related with drug resistance in ESCC. It was noticed that the hsa-miRNA-140-3p (miR-140-3p) expression was considerably higher in drug-resistant cells than in sensitive cells. In addition, DGE identified target genes of miR-140-3p might perform key roles in ESCC. Furthermore, this work exhibited that miR-140-3p represents the nuclear transcription factor Y subunit alpha (NFYA) gene by targeting its 3′-untranslated regions. Such an interaction might influence the formation of the transcription factor NFY trimer, which in turn may inhibit the transcription of the multidrug resistance 1 gene and, ultimately, to multidrug resistance in ESCC. The inhibition of miR-140-3p decreased resistance to oxaliplatin in EC. Therefore, miR-140-3p may serve as a molecular marker for treatment response, efficacy, and prognosis of chemotherapy in ESCC patients.

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Acknowledgements

The authors are thankful to the (1) National Natural Science Foundation of China (No.81703016) and (2) Scientific Research Foundation for Advanced Talents of Bethune Hospital of Shanxi Province (No.2021RC018) for their support to do this research work.

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Author notes

  1. Bin Song and Xiangchen Liu contributed equally.

Authors and Affiliations

  1. Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China

    Bin Song

  2. Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Bin Song

  3. Cancer Center of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China

    Xiangchen Liu

  4. Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Huiling Dong

  5. SHRM Biotechnologies Pvt. Ltd, Kolkata, West Bengal, India

    Rupak Roy

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  1. Bin Song
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Correspondence to Bin Song.

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Song, B., Liu, X., Dong, H. et al. miR-140-3P Induces Chemotherapy Resistance in Esophageal Carcinoma by Targeting the NFYA-MDR1 Axis. Appl Biochem Biotechnol 195, 973–991 (2023). https://doi.org/10.1007/s12010-022-04139-5

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