Evidence map›Paper›PMID 42622908›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Disrupting KRAS-AGO2 interaction: a dual-pronged strategy to sensitize chemo-immunotherapy in KRAS-mutated colorectal cancer.

Jingyi Xie, Simeng Wang, Juan Liu, Yan Zhang, Haixiao Zhu, Rongrong Cui, Yao Yao, Wei Yu, Peng Hou

Abstract read
PubMed Publisher
In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jingyi Xie *Department of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Simeng Wang *Department of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Juan LiuDepartment of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Yan ZhangDepartment of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Haixiao ZhuDepartment of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Rongrong CuiDepartment of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Yao YaoDepartment of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
Wei YuBioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. yuwei4891@xjtufh.edu.cn.
Peng HouDepartment of Endocrinology and Metabolism and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China. phou@xjtu.edu.cn.ORCID https://orcid.org/0000-0001-7010-7944

Funding

Basic Research Plan of Natural Science in Shaanxi Province of China 2024JC-YBMS-661Beijing Natural Science Foundation 7254401Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University XJTU1AF-CRF-2022-009Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University XJTU1AF-CRF-2023-032
6 · The paper itself

Abstract

KRAS mutations are among the most common genetic alterations in colorectal cancer (CRC) and are strongly linked to poor prognosis and therapeutic resistance. However, current treatments targeting KRAS-mutated CRC have shown limited clinical efficacy. Argonaute 2 (AGO2) is a critical component in microRNA (miRNA)-mediated gene silencing complex, which is involved in the maturation of miRNAs and the regulation of target genes. It has been reported that mutated KRAS can interact with AGO2 and impair its function, thereby amplifying the oncogenic potency of mutant KRAS and accelerating tumor progression. To explore the therapeutic implications of this interaction, we developed a peptide inhibitor and engineered peptide-gold nanoparticles (Au-pep) that specifically disrupted KRAS-AGO2 interaction, which dramatically attenuated the malignant phenotype of KRAS-mutated CRC cells. Mechanistically, Au-pep-mediated disruption of the KRAS-AGO2 complex led to partial restoration of the miRNA expression landscape, with let‑7c‑5p emerging as the most significantly up‑regulated effector. As a result, restored let-7c-5p caused a significant down-regulation of key oncogenic drivers (KRAS, c-Myc and Bcl2) to suppress the growth of KRAS-mutated CRC cells and induce their apoptosis. Furthermore, this miRNA restoration conferred dual therapeutic benefits by sensitizing KRAS-mutated CRC cells to 5-fluorouracil (5-FU) via ABCC5 repression and augmenting immunotherapy responsiveness via PD-L1 down-regulation. Our findings, taken together, delineate a new therapeutic paradigm with significant translational potential for improving clinical outcomes in this recalcitrant patient population.

Indexed as

Argonaute ProteinsColorectal NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsApoptosisCell Line, TumorFluorouracilGene Expression Regulation, NeoplasticHumansImmunotherapyMicroRNAsMutationPeptidesAGO2 protein, humanArgonaute ProteinsFluorouracilKRAS protein, humanMicroRNAsmirnlet7 microRNA, humanPeptidesProto-Oncogene Proteins p21(ras)AGO2Chemo-immunotherapy resistanceColorectal cancer (CRC)KRAS mutationsLet-7c-5p

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.