PXD046297-1

PXD046297 is an original dataset announced via ProteomeXchange.

Title	BIN2 Inhibition Suppress Cancer Progression and Protect Ovarian function through Downregulating HDAC1 Phosphorylation
Description	Malignant tumors, or cancers, are increasingly menacing people's life and health. For your female cancer patient, the ideal therapy should achieve dual purpose: suppress tumor progression meanwhile protect ovarian function. We previously showed that activated (phosphorylated) BIN2 in mouse ovaries regulates primordial follicle activation and oocyte quality through p-RPS6, and in this study, we found that BIN2 knockout or inhibition of BIN2 phosphorylation by BPP could suppress the genesis and progression of ovarian cancer. However, in human female ovarian cancer tissues, we didn’t see the increment of p-RPS6 although we observed a significant raise of p-BIN2. From this discrepancy between normal ovaries and ovarian cancer tissue, we guessed that p-BIN2 has other targets that are more important in ovarian cancer progression. Through mass spec identification, we found that only the constitutively active form of BIN2 (T423D & S424D) baits HDAC1, indicating that HDAC1 is a more important target of BIN2 in ovarian cancer. Next, we did saw Bin2 knockout or inhibition significantly decreased p-HDAC1 (S421) meanwhile increased H3K27ac. Moreover, chip seq showed that BIN2 inhibition significantly increased the binding of H3K27ac to multiple tumor suppressors. Besides, BIN2 knockout or inhibition could meanwhile protect ovarian function in mice with chemical carcinogen-induced in-situ ovarian cancers or with ovarian cancer cell transplantation. This study suggested that BIN2 inhibition could both suppress ovarian tumorigenesis and protect ovarian fertility, but through distinct mechanisms.
HostingRepository	iProX
AnnounceDate	2023-10-20
AnnouncementXML	Submission_2023-10-22_19:20:43.162.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Congrong Li
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-22 19:20:26	ID requested
⏵ 1	2023-10-22 19:20:43	announced

Dataset with its publication pending

submitter keyword: BIN2，tumor progression, HDAC1, phosphorylation

Dong Zhang
contact affiliation	Department of Gynaecology and Obstetrics, the First Affiliated Hospital of Anhui Medical University
contact email	dong.ray.zhang@ahmu.edu.cn
lab head
Congrong Li
contact affiliation	Nanjing Medical university
contact email	986162264@qq.com
dataset submitter

iProX dataset URI