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Literature Review | Latest Research by Professor Chen Ming’s Team: miR‑7 May Represent a Novel Therapeutic Target for Inhibiting Prostate Cancer!

Introduction

Prostate cancer (PCa) is a major threat to men’s health worldwide, and 20% to 50% of patients with prostate cancer harbor TP53 mutations. Non-coding R NA, particularly miRNAs, play crucial regulatory roles in tumorigenesis and tumor progression, including in prostate cancer (PCa). Investigating the primary causes of aberrant miRNA expression and the mechanisms by which miRNAs contribute to prostate cancer tumorigenesis will facilitate the development of promising therapeutic strategies.

Recently Professors Chen Ming and Xu Bin of the Zhongda Hospital, affiliated with Southeast University The team published an article titled “Transgenic construction and functional miRNA analysis identify the role of miR-7 in prostate cancer suppression” in the prestigious journal Oncogene (IF = 8.756), revealing… The role of miR‑7 in suppressing prostate cancer has been demonstrated, showing its therapeutic efficacy in p53‑negative tumors and highlighting miR‑7 as a promising target for the development of miRNA‑based therapeutics. 。

Professor Chen Ming

Distinguished Professor of the second level, Chief Physician, Doctoral Supervisor at Southeast University, and Postdoctoral Fellow at Harvard University;

Vice President of the Zhongda Hospital, Affiliated to Southeast University; Director of the Department of Urology; and Director of the Robotic Minimally Invasive Surgery Center.

Director of the Institute of Urology at Southeast University and Director of the Laboratory of the Center for Surgery;

Vice President of the World Association of Chinese Urologists.

Dr. Xu Bin, Doctoral Supervisor

Postdoctoral fellow at the University of Texas MD Anderson Cancer Center;

Deputy Director of the Institute of Urology, Southeast University;

Key medical talent under Jiangsu Province’s 13th Five-Year Plan “Science, Education, and Health Strengthening Project”;

“Six Major Talent Peaks” high-level talent;

Member of the Basic Research Group of the Chinese Society of Urology.

The Institute of Urology at Southeast University is equipped with first‑class cellular and molecular biology facilities. Under the leadership of Professor Ming Chen at the Zhongda Hospital affiliated with Southeast University, the research group currently comprises 15 doctoral students and 38 master’s students. The team is predominantly composed of young researchers, with 100% of its members under the age of 35. Urinary The current research areas of the Institute of Surgery include In all aspects of urinary system diseases, when… Previous research has primarily focused on the immune tolerance–related mechanisms of kidney transplantation, the pathogenesis of urogenital system tumors, and the pathogenesis and treatment of andrological disorders. The laboratory currently undertakes numerous national and provincial key research and development projects. Over the past five years, it has secured more than RMB 15 million in research funding. Since 2021, it has published 52 SCI‑indexed papers, including six with an impact factor greater than 10, and has filed several patent applications. The team has made significant advances in the field of urologic oncology and has received prestigious awards on multiple occasions, such as the Wu Jieping Urology Award and the Golden Bladder Award. Its research has earned widespread recognition from both domestic and international academic communities.

miR‑7 inhibits the progression of prostate cancer and induces an inflammatory immune microenvironment.

Researchers generated transgenic mice that overexpress miR‑7 (miR‑7 ⁺ mice) to investigate the in vivo effects of miR‑7.

Figure 1. Construction of a transgenic mouse model

By comparison, the researchers found that overexpression of miR‑7 promotes inflammation in the immune microenvironment of prostate cancer. Furthermore, miR‑7+/TRAMP mice exhibited a longer survival than TRAMP mice, indicating that miR‑7 exerts an inhibitory effect on prostate cancer in vivo.

Figure 2. miR‑7 inhibits prostate cancer progression in vivo and induces an inflammatory immune microenvironment.

miR‑7 inhibits glycolysis in prostate cancer cells via the HIF‑1α pathway.

Researchers performed RNA sequencing, which revealed that in PCa cells with high miR‑7 expression, metabolism‑related pathways—particularly glycolysis and the HIF‑1α signaling pathway—were significantly downregulated and enriched. The researchers further analyzed the gain‑and‑loss of glycolytic function mediated by miR‑7 in prostate cancer cells, and the results supported the notion that miR‑7 suppresses glycolysis in prostate cancer. To further investigate the direct targets of miR‑7 in prostate cancer (PCa), the researchers performed Venn analysis, Western blotting, and luciferase reporter assays, comparing differentially expressed genes identified by RNA sequencing in miR‑7–treated LNCaP and PC3 cells with the results of online miRDB database analyses.

The results indicate: miR‑7 downregulates glycolysis in prostate cancer through several key pathways, including HIF‑1α. By assessing cell proliferation, colony-forming capacity, apoptosis and cell-cycle progression, as well as analyzing subcutaneous and orthotopic tumor models, we examined the impact of miR‑7 expression on the malignant behavior of prostate cancer (PCa) cells. The results demonstrated that miR‑7 exerts a negative regulatory effect on the malignant phenotypes of PCa cells.

Therapeutic effects of miR‑7 on prostate cancer and lung metastasis in mice

Researchers investigated the therapeutic potential of miR‑7 in prostate cancer using a subcutaneous tumor xenograft model, assessing its tumor‑suppressive effects. Their findings demonstrated that miR‑7 inhibits glycolysis via the HIF‑1α pathway, thereby alleviating the acidic tumor microenvironment and creating favorable conditions for the infiltration of anti‑tumor immune cells. Researchers further In In a mouse model of lung metastasis, combined treatment with miR‑7 and anti‑PD‑1 significantly enhanced therapeutic efficacy in prostate cancer.

Figure 6. Therapeutic effects of miR‑7 on prostate cancer and lung metastasis in mice

The above results demonstrate the therapeutic efficacy of miR‑7 against prostate cancer and lung metastasis in mice, as well as its significant synergistic effect when combined with anti‑PD‑1 therapy.

Through overexpression, it was found that miR‑7 is transcriptionally regulated by p53 in prostate cancer.

To investigate the clinical relevance of miR‑7 in prostate cancer, the researchers performed ISH analysis on large tissue sections and tissue microarrays. Compared with tumor tissues, normal tissues exhibited significantly higher miR‑7 expression, a finding that was further confirmed by qRT‑PCR. Further analysis using the TCGA database in conjunction with LASSO regression yielded a prognostic signature comprising nine miR‑7‑related genes, which served as an independent predictor of progression-free survival (PFS) in the TCGA cohort. This signature demonstrated relatively high predictive accuracy for 1‑year (AUC = 0.85), 3‑year (AUC = 0.79), and 5‑year (AUC = 0.74) PFS.

In summary, the above findings demonstrate that p53 upregulates miR‑7, suggesting that miR‑7 could be a promising target for the development of miRNA‑based therapeutics, particularly for PCa patients harboring p53 mutations. These results underscore that, regardless of p53 status, the development of miRNA‑based therapies for prostate cancer represents a highly promising avenue. Throughout critical steps—including the establishment of TRAMP mouse models and the generation and breeding of miR‑7 transgenic mice—Aniphe BioLab played a pivotal role.

Source: https://doi.org/10.1038/s41388-022-02461-0

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