Distinct miR319a Identified from Persicaria chinensis Mediates Cross-Kingdom Suppression of Cervical Cancer by Targeting ITGA3

Abstract

Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.

1. Introduction

Cervical cancer is the second most common cancer among women in low- and lower-middle-income countries, posing a significant threat to public health [1,2]. The management of cervical cancer is confronted with several formidable challenges, including drug resistance, metastasis, and recurrence [3]. Consequently, the development of novel therapeutic strategies, particularly those based on natural products, has become a focal point of current research. Natural products, especially traditional Chinese medicinal herbs, are recognized for their potential to modulate critical molecular pathways involved in tumor proliferation inhibition, attributable to their complex chemical constituents and diverse biological activities [4,5]. Notwithstanding the demonstration of promising antitumor properties in preclinical studies, traditional Chinese medicinal herbs remain underutilized in the clinical treatment of cervical cancer, and their underlying mechanisms of action have yet to be fully elucidated.

Persicaria chinensis (L.) H. Gross, also known as Polygonum chinense, has versatile culinary and medicinal uses. It can be brewed into herbal tea with a slightly sour flavor, offering benefits for dampness removal and summer heat relief [6]. As a perennial herb widely distributed in southern China, it has also been used in traditional medicine to treat inflammatory disorders and tumors for centuries. Modern pharmacological studies have revealed that P. chinensis is rich in flavonoids, coumarins, and phenolic acids, exhibiting anti-inflammatory, antioxidant, and antitumor activities [6–10]. For instance, phenolic substances, such as ellagic acid and corilagin, significantly inhibit the proliferation of cervical cancer SiHa cells and induce apoptosis by upregulating the protein expression levels of p53, Bcl-2, and caspase-3/9 while concurrently downregulating the protein expression level of Bax [11]. However, the short half-life of small molecules in P. chinensis significantly restricts their efficacy and durability in the treatment of chronic diseases.