MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2

Xiaowen Cao; Fangsu Xue; Haoyu Chen; Lu Shen; Xiaosa Yuan; Yunchi Yu; Ying Zong; Lou Zhong; Fang Huang

doi:10.21037/atm-22-6089

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2

Ann Transl Med. 2022 Dec;10(24):1374. doi: 10.21037/atm-22-6089.

Authors

Xiaowen Cao^#¹, Fangsu Xue^#², Haoyu Chen¹, Lu Shen¹, Xiaosa Yuan¹, Yunchi Yu¹, Ying Zong³, Lou Zhong¹, Fang Huang⁴

Affiliations

¹ Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
² Department of Respiration, Binhai County People's Hospital, Yancheng, China.
³ Medical College of Nantong University, Nantong, China.
⁴ Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.

^# Contributed equally.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis is still unclear. The present study aimed to investigate the role of miR-202-3p and its downstream target gene, ribonucleotide reductase regulatory subunit M2 (RRM2), in the occurrence and development of LUAD and elucidate the correlation between RRM2 and the clinicopathological stage and prognosis of LUAD.

Methods: The expression of miR-202-3p was analyzed using the CancerMIRNome database and quantitative polymerase chain reaction (qPCR). The effects of miR-202-3p and RRM2 on the proliferation, migration, and invasion of A549 cells were analyzed. A dual luciferase reporter assay was used to verify the targeting of miR-202-3p and RRM2. Additionally, the correlation between RRM2 expression and clinicopathology was analyzed.

Results: (I) MiR-202-3p was lowly expressed in LUAD and the LUAD cell lines. qPCR confirmed that microRNA (miRNA) transfection was effective and sufficient for subsequent experiments. (II) MiR-202-3p inhibited the proliferation, invasion, and migration of LUAD cells. (III) There was a targeting relationship between miR-202-3p and RRM2, and miR-202-3p affected the expression of the RRM2 protein. RRM2 was highly expressed in lung cancer tissue. (IV) RRM2 was associated with the clinicopathological staging of lung cancer. The prognosis of patients with low RRM2 expression was better, and the prognostic sensitivity of RRM2 to lung cancer was high. RRM2 may exert its effects via the Notch pathway. (V) Si-RRM2 inhibited the expression of the RRM2 protein. RRM2 promoted the proliferation, migration, and invasion of LUAD cells. A miR-202-3p inhibitor restored the inhibitory effect of si-RRM2 on LUAD cells.

Conclusions: MiR-202-3p was lowly expressed in lung cancer tissue. MiR-202-3p overexpression inhibited the proliferation and metastasis of lung cancer cells. RRM2 was highly expressed in lung cancer tissue and promoted the proliferation and metastasis of lung cancer cells. MiR-202-3p targeted and inhibited RRM2, thereby reducing the proliferation and metastasis of LUAD cells. LUAD patients with low RRM2 expression had a better prognosis, and the expression level of RRM2 was correlated with the clinical characteristics of lung cancer patients.

Keywords: Lung adenocarcinoma (LUAD); metastasis; miR-202-3p; proliferation; ribonucleotide reductase regulatory subunit M2 (RRM2).