LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression

Sep 24, 2026

This study investigates how LRRC75A-AS1 delivered by M2 macrophage exosomes contributes to cervical cancer progression. LRRC75A-AS1 is highly expressed in exosomes from M2 macrophages and can be absorbed by Hela cells. These exosomes enhance proliferation, migration, invasion, and EMT, while LRRC75A-AS1 directly suppresses miR-429. miR-429 modulates SIX1 and affects STAT3/MMP-9 signaling, reducing tumor formation and metastasis in nude mice; the effects are reversed by LRRC75A-AS1-overexpressing exosomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Introduction

Received: 24 July 2022 | Revised: 13 February 2023 | Accepted: 22 February 2023 DOI: 10. 1111/cas.15780 OR I G I NAL ART I C L E LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression Hong-Ying Sui1 | Xiu-Ying Cui2 | Cai-Xia Shi1 | Zhi-Peng Yan1 | Hu-Cheng Li1 | Fang Wang1 1The Department of Gynecological Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China 2The department of gyneacology, People's Hospital of Turpan City, Turpan, China Correspondence Hong-Ying Sui, The Department of Gynecological Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, No. 283, Tongzipo Road, Yuelu District, Changsha 410013, HN, China. Email: [hhooyyssu987@163.com](hhooyyssu987@163.com) Funding information The funding project of Turpan Science and Technology Bureau, Grant/Award Number: 2019BJ001; Key R&D Project of Scientific Research Climbing Plan of Hunan Cancer Hospital, Grant/Award Number: YF2020003; National Cancer Center Climbing Fund, Grant/Award Number: NCC2018B66 Abstract We aimed to investigate potential roles of LRRC75A-AS1 delivered by M2 macrophage exosomes in inducing cervical cancer progression. We demonstrated LRRC75A-AS1 was highly expressed in exosomes from M2 macrophages which could be absorbed by Hela cells. M2 macrophage-derived exosomes promoted Hela cell proliferation, migration, invasion, and EMT process by delivering LRRC75A-AS1 . LRRC75A-AS1 directly targeted and suppressed miR-429 in Hela cells. The regulation of cell functions by exosomes from LRRC75A-AS1-overexpressing M2 macrophages was abrogated by miR-429 mimics. miR-429 directly targeted and repressed SIX1 expression. SIX1 overexpression alleviated the modulation of cellular functions and STAT3/MMP-9 signaling by miR-429 mimics. Also, miR-429 overexpression or SIX1 silence repressed tumor formation and metastasis in nude mice, which was mitigated by exosomes from LRRC75A-AS1-overexpressing M2 macrophages. In conclusion, LRRC75A-AS1 delivered by M2 macrophage exosomes repressed miR-429 to elevate SIX1 expression and promote cervical cancer progression through activating the STAT3/MMP-9 axis. K E Y WO R D S cervical cancer, exosomes, LRRC75A-AS1, M2 macrophages, miR-429, SIX1 1 | INTRODUCTION Cervical cancer is a major malignant cancer in females worldwide, which is estimated to cause more than 260, 000 deaths each year.1–3 The majority of cervical cancer cases are mainly attributed to the persistent infection with human papilloma virus (HPV), as well as other risk factors such as smoking and sexual activities. 2,4,5 The application of early screening and HPV vaccines has greatly reduced the incidence and mortality of cervical cancer.1,3 However, its incidence still remains high, wherein 15% of cervical cancer patients are usually diagnosed at advanced stages with lymphatic or hematogenous metastasis.6 Even worse, metastatic patients are commonly not Abbreviations: Arg-1, arginase-1; CRKL, Crk-like adapter protein; EMT, epithelial to mesenchymal transition; HPV, human papilloma virus; LRRC75A-AS1, the antisense of leucine-rich repeat-containing protein 75A; MMP-9, matrix metalloproteinase 9; NTA, nanoparticle tracking analysis; PMA, phorbol 12-myristate 13-acetate; SIX1, sine oculis homebox 1; SPF, specific pathogen-free; STAT3, signal transducer and activator of transcription 3; TEM, transmission electron microscopy; TGF-β1, transforming growth factor β1; ZEB1, zinc finger E-box binding homeobox 1. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2023 The Authors. Cancer Sc

FAQs

What is the molecular pathway connecting miR-429, SIX1, and STAT3/MMP-9?

miR-429 directly targets and represses SIX1 expression. SIX1 overexpression alleviates the modulation of cellular functions and STAT3/MMP-9 signaling caused by miR-429 mimics, promoting or restoring the cancer-promoting phenotype.

Sep 24, 2026

Uploaded by Valentina