TY - JOUR
T1 - Effects of let-7a microRNA and C–C chemokine receptor type 7 expression on cellular function and prognosis in esophageal squamous cell carcinoma
AU - Yura, Masahiro
AU - Fukuda, Kazumasa
AU - Matsuda, Satoru
AU - Irino, Tomoyuki
AU - Nakamura, Rieko
AU - Kawakubo, Hirofumi
AU - Takeuchi, Hiroya
AU - Kitagawa, Yuko
N1 - Funding Information:
We acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 51825905, U1865204, 52179141), Major Science and Technology Special Program of Yunnan Province (202202AF080004), YaLong River Hydropower Development Co., Ltd., Swansea University, (0023-20XJ0011) and science project of China Huaneng Group Co. Ltd,HNKJ18-H26.The numerical calculations in this work have been done on the supercomputing system in the Supercomputing Center of Wuhan University.
Funding Information:
The authors would like to thank Mrs. Satsuki Fukuhara of the Keio University School of Medicine for her valuable advice regarding the experiments in this study.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - C–C chemokine receptor type 7
KW - Esophageal squamous cell carcinoma
KW - Invasive ability
KW - Let-7a microRNA
KW - Metastasis
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U2 - 10.1186/s12885-022-10178-2
DO - 10.1186/s12885-022-10178-2
M3 - Article
C2 - 36243683
AN - SCOPUS:85139853020
SN - 1471-2407
VL - 22
JO - BMC cancer
JF - BMC cancer
IS - 1
M1 - 1064
ER -
