Effects of let-7a microRNA and C–C chemokine receptor type 7 expression on cellular function and prognosis in esophageal squamous cell carcinoma

Masahiro Yura, Kazumasa Fukuda, Satoru Matsuda, Tomoyuki Irino, Rieko Nakamura, Hirofumi Kawakubo, Hiroya Takeuchi, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

Abstract

Background: C–C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression. Methods: The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis. Results: A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups. Conclusions: The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients. Trial registration. Retrospectively registered.

Original languageEnglish
Article number1064
JournalBMC cancer
Volume22
Issue number1
DOIs
Publication statusPublished - 2022 Dec

Keywords

  • C–C chemokine receptor type 7
  • Esophageal squamous cell carcinoma
  • Invasive ability
  • Let-7a microRNA
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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