Jho Published: Overcoming a new mechanism for triple -negative breast cancer!

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J Hematol Oncol: The ring RNA is assembled by destroying PKR stability and inhibiting tri -negative breast cancer stress and overcoming the resistance of Aycin

▎ Clinical issue:

Circle RNA (CIRCRNAS) is a new type of regulatory RNA with high evolution conservativeness and stability. CIRCRNAS is expected to become a potential diagnosis of biomarkers and therapeutic targets for a variety of malignant tumors. However, CirCRNAS's regulatory function and potential mechanisms in trio -breast cancer (TNBC) are largely unknown.

The latest research screening and verification of breast cancer (BC) and TNBC tissue in the J Hematol Oncol journal, and the specific regulatory mechanism of regulating abnormalities in TNBC tissue.

▎ Research plan:

Researchers use RNA high-throughput sequencing technology, QRT-PCR and in-situ hybrid technology to screen CirCRNAS. Then use in vitro experiments, animal models, and patients from patients (PDOS) to explore the role of candidate CirCRNAS in TNBC. In order to study its potential mechanisms, RNA drop-down experiments, RNA immune sedimentation (RIP), co-immune precipitation (CO-IP), and protein printing method.

▎ Main discovery:

This study proves that CirCRNA-CREIT is abnormally lowered in the TNBC cells of ascinin, and is related to bad prognosis.

The RNA binding protein DHX9 interacts with the opposite repetitive ALU (iralu) sequence of the wing, and inhibits reverse editing, thereby reducing the expression of CirCRNA-CREIT.

Through in vitro experiments, animal models, and patients from the source of patients, it was found that CirCRNA-CREIT's expression significantly enhanced the sensitivity of TNBC cells to corneurin.

In terms of mechanism, CirCRNA-CREIT promotes the interaction between PKR and E3 connection enzyme hace1 as a bracket, and promotes PKR protein degradation through multipotrauminization connected by K48.

The decrease in PKR/EIF2α signal axis is considered to be the key downstream effect of CirCRNA-CREIT. Its weakened stress particles (SGS) assembly to activate RACK1/MTK1 apoptotic signal channels.

Further studies have shown that SG inhibitors ISRIB and eycinicin are combined with coordinated inhibitory TNBC tumor growth.

In addition, CirCRNA-CREIT can be wrapped into the exosten body, making TNBC cells sensitive to corneumin.

▎ Looking out:

This study shows that targeting CirCRNA-CREIT and SGS can be used as an effective strategy for treating TNBC chemotherapy resistance.

references:

[1] https://jhoonline.biomedCentral.com/articleS/10.1186/s13045-022-01345-w

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