# Research and progress of microRNA-136 in metastatic tumors

**Authors:** Chenwen Wang, Zixiong Chen, Wei Ni, Jiang Wang, Wei Zhou

PMC · DOI: 10.3389/fonc.2025.1555270 · Frontiers in Oncology · 2025-03-04

## TL;DR

This review explores how miR-136, a microRNA, influences cancer growth, spread, and treatment resistance, suggesting it could be a new target for cancer therapy.

## Contribution

The paper provides a comprehensive review of miR-136's roles in multiple cancers and its potential as a therapeutic target.

## Key findings

- MiR-136 acts as a tumor suppressor by targeting genes like MTDH, PTEN, and MAP2K4.
- It influences key signaling pathways such as ERK, Wnt/β-catenin, and PI3K/Akt.
- MiR-136 is involved in chemoresistance through mechanisms like the miR-136-Notch3 axis.

## Abstract

MiR-136 is abnormally expressed in many types of metastatic tumors and is closely associated with tumor cell proliferation, apoptosis, invasion, and metastasis, indicating its important role in tumor development and progression. This review summarizes current knowledge regarding miR-136’s molecular mechanisms, functional roles, and impact on chemotherapy in different human cancers.

A literature search was conducted in PubMed and Web of Science using “miR-136” and “metastatic tumors” as English keywords, and in CNKI and Wanfang databases using the same terms in Chinese. Studies related to miR-136 research in metastatic tumors and high-quality evidence from similar studies were included. Meta-analyses, dissertations, conference papers, low-quality articles, unavailable full-text articles, and republished articles were excluded.

This review synthesizes the current understanding of miR-136’s role in various cancers, including osteosarcoma, gastric cancer, gallbladder cancer, esophageal cancer, prostate cancer, colorectal cancer, breast cancer, glioma, and thyroid cancer. miR-136 acts as a tumor suppressor by targeting various genes, including MTDH, PTEN, MAP2K4, MUC1, LRH-1, MIEN1, RASAL2, CYR61, and KLF7. It influences multiple signaling pathways, including the ERK/mitogen-activated protein kinase, Wnt/β-catenin, Ha-Ras, PI3K/Akt, Aurora-A kinase, nuclear factor-κB, and JNK pathways. Furthermore, miR-136 is involved in chemoresistance by modulating ROCK1, PPP2R2A, and the miR-136-Notch3 signaling axis.

MiR-136 demonstrates promising potential as a novel biomarker and therapeutic target in various human cancers. Further research is needed to fully elucidate its complex roles in cancer development, progression, and drug resistance, particularly regarding its potential in immunotherapy.

## Linked entities

- **Genes:** MTDH (metadherin) [NCBI Gene 92140], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], MAP2K4 (mitogen-activated protein kinase kinase 4) [NCBI Gene 6416], MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582], NR5A2 (nuclear receptor subfamily 5 group A member 2) [NCBI Gene 2494], MIEN1 (migration and invasion enhancer 1) [NCBI Gene 84299], RASAL2 (RAS protein activator like 2) [NCBI Gene 9462], CCN1 (cellular communication network factor 1) [NCBI Gene 3491], KLF7 (KLF transcription factor 7) [NCBI Gene 8609], ROCK1 (Rho associated coiled-coil containing protein kinase 1) [NCBI Gene 6093], PPP2R2A (protein phosphatase 2 regulatory subunit Balpha) [NCBI Gene 5520]
- **Diseases:** osteosarcoma (MONDO:0002623), gastric cancer (MONDO:0001056), gallbladder cancer (MONDO:0003220), esophageal cancer (MONDO:0007576), prostate cancer (MONDO:0005159), colorectal cancer (MONDO:0005575), breast cancer (MONDO:0004989), glioma (MONDO:0021042), thyroid cancer (MONDO:0002108)

## Full-text entities

- **Genes:** KLF7 (KLF transcription factor 7) [NCBI Gene 8609] {aka UKLF}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PPP2R2A (protein phosphatase 2 regulatory subunit Balpha) [NCBI Gene 5520] {aka B55, B55A, B55ALPHA, PR52A, PR55A, PR55alpha}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, MAP2K4 (mitogen-activated protein kinase kinase 4) [NCBI Gene 6416] {aka JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4}, NR5A2 (nuclear receptor subfamily 5 group A member 2) [NCBI Gene 2494] {aka B1F, B1F2, CPF, FTF, FTZ-F1, FTZ-F1beta}, NOTCH3 (notch receptor 3) [NCBI Gene 4854] {aka CADASIL, CADASIL1, CARASIL1, CASIL, FPLD1, IMF2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MTDH (metadherin) [NCBI Gene 92140] {aka 3D3, AEG-1, AEG1, LYRIC, LYRIC/3D3}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, ROCK1 (Rho associated coiled-coil containing protein kinase 1) [NCBI Gene 6093] {aka P160ROCK, ROCK-I}, RASAL2 (RAS protein activator like 2) [NCBI Gene 9462] {aka NGAP}, MIR136 (microRNA 136) [NCBI Gene 406927] {aka MIRN136, miRNA136, mir-136}, MIEN1 (migration and invasion enhancer 1) [NCBI Gene 84299] {aka C17orf37, C35, ORB3, RDX12, XTP4}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}
- **Diseases:** thyroid cancer (MESH:D013964), glioma (MESH:D005910), colorectal cancer (MESH:D015179), prostate cancer (MESH:D011471), esophageal cancer (MESH:D004938), osteosarcoma (MESH:D012516), metastasis (MESH:D009362), gastric cancer (MESH:D013274), breast cancer (MESH:D001943), gallbladder cancer (MESH:D005706), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

90 references — full list in the complete paper: https://tomesphere.com/paper/PMC11913677/full.md

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Source: https://tomesphere.com/paper/PMC11913677