The Role of miRNAs in the Treatment and Regulation of

Gastrointestinal Tumors

Weixiao Yuan

Hangzhou Xizi Experimental School, Hangzhou, China

Keywords: miRNA, Gastrointestinal Tumors, Biomarker.

Abstract: MicroRNA (miRNA) is a class of endogenous non-coding small RNA molecules that regulate gene expression

at the post-transcriptional level by partially complementary binding to the 3'untranslated region (3'UTR) of

target mRNA. This review summarizes miRNA's biogenesis and regulatory mechanisms, detailing the entire

process from transcription and processing to maturation and functional exertion within the cell. Studies have

shown that miRNA plays a crucial role in cell development, differentiation, proliferation, apoptosis, disease

occurrence, and immune regulation. The development and progression of gastrointestinal tumors is a complex,

multifactorial, and multistage process involving genetic factors, environmental factors, lifestyle, microbial

infections, and precancerous lesions. Tumor cells promote their growth, invasion, and metastasis through

genetic mutations, clonal evolution, and dynamic changes in the tumor microenvironment. This paper further

explores the regulatory role of miRNA in gastrointestinal tumors and finds that specific miRNAs (such as

miR-221, miR-125b, miR-320a-3p, etc.) significantly affect the progression of gastrointestinal tumors by

regulating cell proliferation, apoptosis, metastasis, and invasion. In addition, miRNA, due to its stability and

ubiquity in various biological fluids, shows potential as a tumor biomarker for early diagnosis and monitoring

of tumor progression. Meanwhile, miRNA further influences tumor growth and development by regulating

cells and metabolites in the tumor microenvironment. miRNA has excellent potential for application in

controlling and treating gastrointestinal tumors. With the continuous progress of research and technology,

miRNA is expected to become an essential tool for diagnosing and treating gastrointestinal tumors, providing

new strategies and hope for cancer patients.

1 INTRODUCTION

As modern health issues gradually come to the

forefront, gastrointestinal health problems among the

Chinese population have become particularly

prominent. The Chinese preference for greasy and

salty foods has led to a significant burden on their

gastrointestinal system, posing a considerable risk to

their gastrointestinal health, with gastrointestinal

tumors being especially typical. According to data

from the National Cancer Center, in 2024, the annual

incidence of gastric cancer in China exceeded 350,000

cases, ranking 5th among all malignant tumors; the

number of deaths exceeded 260,000, ranking 3rd

among malignant tumors. Chinese gastric cancer

patients account for approximately 40%of the global

total. This highlights the urgent need to pursue

effective treatments and methods for gastrointestinal

diseases, especially major diseases such as

gastrointestinal tumors. The significant advancements

in biology in recent years may have unveiled a glimpse

into treating gastrointestinal tumors.

In 2024, the Nobel Prize in Physiology or

Medicine was awarded to American scientist Victor

Ambros and biologist Gary Ruvkun for discovering

microRNA and its role in post-transcriptional gene

regulation. MicroRNA is a type of RNA molecule

transcribed from DNA, which regulates gene

expression by affecting other RNA molecules

transcribed from DNA. After the discovery of

microRNA was made public, its immense potential in

the medical field, especially in cancer treatment, was

quickly recognized. The abnormal expression of

oncogenes and tumor suppressor genes causes the

emergence of cancer. If microRNA could regulate the

expression of oncogenes and tumor suppressor genes

in cancerous cells, treating cancer with microRNA

would become a viable approach. Research has found

that microRNA molecules such as microRNA-25,

microRNA-451, and microRNA-625 play various

Yuan, W.

The Role of miRNAs in the Treatment and Regulation of Gastrointestinal Tumors.

DOI: 10.5220/0014464600004933

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 207-211

ISBN: 978-989-758-789-4

207

roles in treating colorectal cancer. Therefore,

microRNA has become a hot topic in colorectal cancer

treatment. However, current research on microRNA is

still relatively limited. As an emerging field, there are

many unexplored areas, and the study of microRNA

has a broad prospect for research and application. This

study systematically analyzed the role and impact of

microRNA in colorectal cancer by organizing and

analyzing data, elucidating the mechanisms and

pathways of microRNA in the development and

metastasis of colorectal cancer, and providing a

foundational plan for different stages of colorectal

cancer diagnosis and treatment.

2 BIOGENESIS AND

REGULATORY MECHANISMS

OF MICRORNA

The miRNA coding sequence is first transcribed into

an extended primary transcript (pri-miRNA) by RNA

polymerase II (Pol II) (Emily et al. 2025), which is

the unprocessed primary miRNA and typically

features a polyadenylated 3'end and a 5'cap structure.

The nascent pri-miRNA is cleaved by a

microprocessor complex (composed of Drosha and

DGCR8) near the junction between single-stranded

RNA (ssRNA) and the dsRNA hairpin (referred to as

the basal junction) into a precursor miRNA called

pre-miRNA (Truong et al. 2024). This pre-miRNA is

a hairpin-shaped precursor miRNA with a length of

approximately 70 nucleotides. It is then explicitly

recognized and bound by the nuclear export protein

Exportin-5, mediating the atomic export of pre-

miRNA precursors(pre-miRNAs) (Wang 2020). The

pre-miRNA is recognized and bound by the

ribonuclease Dicer in the cytoplasm. Dicer's C-

terminal double-stranded RNA-binding domain

(dsRBD) recognizes the GYM motif (Lee et al. 2023).

After processing by Dicer, a small interfering RNA

(siRNA) with a length of about 21–23 nucleotides is

formed, completing the second processing of miRNA

within the cell. Some pre-miRNAs are directly

processed into mature miRNAs by Dicer. One strand

of the siRNA, the guide strand, is loaded into the

RNA-induced Silencing Complex (RISC), which

plays a crucial role in both the small interfering RNA

(siRNA) and microRNA(miRNA)pathways (Zhang

et al. 2018). The other strand, the passenger strand

(which is usually degraded), is ultimately wholly

processed into the fully mature miRNA. Mature

miRNAs play critical regulatory roles within the cell.

If miRNAs are not entirely complementary to their

target RNAs, they will inhibit the translation process,

affecting peptide bond formation and ultimately

reducing the expression of the corresponding

proteins. When miRNAs are fully or almost entirely

complementary to their target mRNAs, they can lead

to the degradation of the target mRNA (this

mechanism is more common in plants than animals).

miRNAs play a crucial role in cell development and

differentiation, cell proliferation and apoptosis,

disease occurrence and immune regulation. This

paper will focus on disease occurrence and cellular

physiological mechanisms.

3 OCCURRENCE AND

DEVELOPMENT OF

GASTROINTESTINAL

TUMORS

Genetic factors, microbial factors, environmental and

lifestyle factors, and precancerous lesions are several

of the main factors contributing to gastrointestinal

tumors. Genetics is essential, as both gastric and

colorectal cancers exhibit familial clustering.

Mutations in genes such as BRCA1/2 and MLH1 are

closely related to the occurrence of gastrointestinal

cancer. Abnormal expression of MLH1 is associated

with gene mutations and methylation, which may lead

to a lack of mismatch repair (MMR) and subsequent

malignant transformation of cells (Tian et al. 2025).

Variants of BRCA1 and BRCA2 (Matykiewicz et al.

2025) also have many cancer risk factors. The intake

of nitrites and polycyclic aromatic hydrocarbons,

which are carcinogens found in high-salt pickled

foods, increases the risk of gastrointestinal tumors.

Fresh vegetables and fruits rich in vitamin C can

block the synthesis of nitrosamines, thereby reducing

the incidence of tumors. Harmful substances such as

nicotine ingested through smoking can damage the

gastrointestinal mucosa, reduce the body's immune

capacity, and promote tumor development. In

addition, dysbiosis of the gut microbiota and

infections with Fusobacterium nucleatum and

Helicobacter pylori can promote inflammatory

responses, tumor development, and the conversion of

nitrates to nitrites and nitrosamines. Helicobacter

pylori has been classified as a Group 1 carcinogen by

the International Agency for Research on Cancer and

the World Health Organization, and its infection is

considered a significant risk factor for gastric cancer

(GC) (Liu et al. 2024). Some precancerous lesions,

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

208

such as chronic atrophic gastritis, gastric polyps, and

gastric ulcers, may gradually evolve into gastric

cancer.

In the development of gastrointestinal tumors,

gene mutations and clonal evolution, the role of the

tumor microenvironment, and metastasis and

recurrence are essential influencing factors. Early

tumor cells, such as cancer-associated fibroblasts and

immune cells, accumulate sufficient growth

advantages through gene mutations. As they grow,

tumor cells accumulate more neutral mutations,

leading to advanced tumors. Cells in the tumor

microenvironment and metabolites such as lactate

and glutamine provide essential carbon and nitrogen

sources to sustain the growth of cancer cells, which

can promote tumor growth, invasion, and metastasis

during tumor development (Huang et al. 2024).

Tumors can also metastasize through body fluids such

as blood and lymph, leading to tumor recurrence.

Gastrointestinal tumors trigger their occurrence and

development through the above methods. Introducing

miRNA regulation in this process can inhibit one or

several links in the development of gastrointestinal

tumors, thereby affecting the entire tumor occurrence

and development process.

4 REGULATORY AND

THERAPEUTIC ROLES OF

MICRORNA IN THE

OCCURRENCE AND

DEVELOPMENT OF

GASTROINTESTINAL

TUMORS

During the occurrence and development of

gastrointestinal tumors, miRNA plays a vital role in

regulating cell proliferation and apoptosis. In

promoting cell proliferation, miR-221 promotes cell

cycle progression by targeting proteins, thereby

facilitating cell proliferation. The expression level of

miR-221 may be closely related to the occurrence and

development of gastric cancer, and a series of miRNA

genes such as miR-221 may become an essential

target for the diagnosis and treatment of gastric

cancer and other digestive tract and organ tumors in

the future (Tao et al. 2010). In regulating apoptosis,

miR-125b targets Bcl-2 family proteins to inhibit cell

proliferation and induce apoptosis. In regulating

tumor metastasis and invasion, some miRNAs

promote the metastasis and invasion of

gastrointestinal tumor cells by regulating genes

related to epithelial-mesenchymal transition. For

example, miR-320a-3p is downregulated in many

tumors, and its downregulation is associated with

enhanced invasion and migration capabilities of

tumor cells. MicroRNA 320a-3p may become a

potential target for GC immunotherapy by inhibiting

PD-L1 gene expression (Asghariazar et al. 2025).

Therefore, enhancing the expression of miRNAs that

inhibit tumor cell proliferation and metastasis and

promote tumor cell apoptosis through genetic

engineering may help control the progression of

gastrointestinal tumors.

MicroRNAs are abnormally expressed in many

gastrointestinal tumors, so they can be used as a

detection marker to reflect the development status of

tumors and thus serve as a tumor marker for auxiliary

diagnosis. MicroRNAs are considered promising

candidates for clinical biomarkers because of their

stable characteristics and ubiquity in easily accessible

biofluids obtained through non-invasive and

minimally invasive means (Metcalf et al. 2024).

Studies have shown that tumor-specific DNA and

RNA are often found in the plasma of cancer patients

(Metcalf et al. 2024) and can be used as potential

tumor markers for early diagnosis. In addition,

miRNAs can also be used as therapeutic agents to

complement the treatment of gastrointestinal tumors.

For example, miRNA-34a exhibits significant tumor-

suppressive effects in gastric cancer and can serve as

a targeted therapy. Moreover, miRNAs can regulate

the tumor microenvironment to affect tumor

progression. For example, cancer-associated

fibroblasts (CAFs) play an essential role in the tumor

microenvironment, and miRNAs can influence tumor

growth and development by controlling the

interaction between CAFs and tumor cells (Nedaeinia

et al. 2024). On the other hand, miRNAs can also be

combined with other therapeutic methods for

combined tumor therapy. Studies have found that

miRNAs are promising immunotherapy adjuvants

that can enhance the effectiveness of tumor treatment

(Yadav et al. 2024).

5 OUTLOOK ON THE

APPLICATION OF MICRORNA

IN THE TREATMENT OF

GASTROINTESTINAL

TUMORS

Many miRNA molecules have been found to regulate

tumor cells, so using miRNA for tumor treatment has

The Role of miRNAs in the Treatment and Regulation of Gastrointestinal Tumors

209

a broad prospect and promotes cancer treatment

research. However, although researchers have

achieved phased results in the regulatory

mechanisms, functional analysis, and tumor

association of miRNA, many fundamental scientific

issues in this field have not been clarified. First, the

expression regulation network of miRNA itself has

not been fully explained, and the molecular

mechanisms of its transcriptional activation or

inhibition still need to be further explored. Secondly,

there is still a lack of systematic research evidence on

whether the regulatory role of miRNA in tumor

occurrence and development is tissue-specific or

universally associated with everyday cell

physiological activities and other disease processes.

The unresolved nature of these core issues indicates

that miRNA-related research still needs a long period

of theoretical exploration and technological

breakthroughs. In addition, how to transform the

regulatory mechanisms of miRNA on gastrointestinal

tumors into clinically operable diagnostic and

therapeutic strategies remains a key direction for

translational medical research. Therefore, promoting

the transformation of basic research results into

clinical treatment has become an important

development direction in this field.

6 CONCLUSION

MicroRNA (miRNA), as a class of crucial molecules

regulating gene expression, has demonstrated

significant potential in the occurrence, development,

and treatment of gastrointestinal tumors. By

controlling biological processes such as cell

proliferation, apoptosis, metastasis, and invasion,

miRNA plays a vital role in tumor progression.

Studies have found that specific miRNAs (such as

miR-221, miR-125b, miR-320a-3p, etc.) are

abnormally expressed in gastrointestinal tumors and

are closely related to the biological behavior of

tumors. In addition, due to their stability and

widespread presence in various biological fluids,

miRNAs are considered to have the potential as tumor

biomarkers for early diagnosis and monitoring of

tumor progression. MiRNAs can also serve as

therapeutic targets; by regulating their expression or

function, tumor cell proliferation, metastasis, and

invasion can be inhibited, and cell apoptosis can be

induced. For example, miRNA-34a exhibits

significant tumor-suppressive effects in gastric

cancer, revealing its potential as a targeted

therapeutic approach. Moreover, miRNAs can

influence tumor growth and development by

regulating cells (such as cancer-associated

fibroblasts) and metabolites (such as glutamine) in the

tumor microenvironment, providing new ideas for

comprehensive treatment.

Although significant progress has been made in

the study of miRNA in gastrointestinal tumors, it is

still in its infancy, and many key issues remain

unresolved. For example, the regulatory mechanisms

of miRNA expression, its specific role in

tumorigenesis, and how to translate research findings

into clinical applications are still pressing issues.

Future research directions should include: in-depth

exploration of the regulatory mechanisms of miRNA

and its specific role in tumorigenesis; development of

efficient miRNA delivery systems for precise

treatment; investigation of the combined application

of miRNA with other therapeutic approaches (such as

chemotherapy and immunotherapy) to enhance

therapeutic effects; and validation of miRNA as a

tumor biomarker and therapeutic target through large-

scale clinical trials. In summary, miRNA has

excellent potential for application in regulating and

treating gastrointestinal tumors. With the continuous

progress of research and technology, miRNA is

expected to become an essential tool for diagnosing

and treating gastrointestinal tumors, bringing new

hope to cancer patients.

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