SNRPD1 conveys prognostic value on breast cancer survival and is required for anthracycline sensitivity

• Published in: BMC cancer Vol. 23; no. 1; p. 376
• Main Authors: Dai, Xiaofeng, Cai, Linhan, Zhang, Zhifa, Li, Jitian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25-04-2023; BioMed Central; BMC
• Subjects: Analysis; Angiogenesis; Anthracycline; Anthracycline resistance; Anthracyclines; Anthracyclines - pharmacology; Anthracyclines - therapeutic use; Antibiotics, Antineoplastic - pharmacology; Antibiotics, Antineoplastic - therapeutic use; Breast - pathology; Breast cancer; Carcinogenesis; Care and treatment; Cell cycle; Cell differentiation; Cell Line, Tumor; Cell migration; Cell proliferation; Chemotherapy; Clinical outcome; Complications and side effects; Datasets; Disease; Dosage and administration; Doxorubicin; Drug development; Drug sensitization; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic analysis; Genomes; Genomics; Genotype & phenotype; Health aspects; Homeopathy; Humans; Mass spectrometry; Materia medica and therapeutics; Metastasis; Mutation; Prevention; Prognosis; Prognostic value; Proteins; Quantitative genetics; Quantitative trait loci; Risk factors; Scientific imaging; SNRPD1; Therapeutic targets; Therapeutics; Treatment Outcome; Triple negative breast cancer; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; China; Germany; Anthracycline resistance; Prognostic value; Clinical outcome; SNRPD1; Triple negative breast cancer
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10860-z

Cancers harboring spliceosome mutations are highly sensitive to additional perturbations on the spliceosome that leads to the development of onco-therapeutics targeting the spliceosome and opens novel opportunities for managing aggressive tumors lacking effective treatment options such as triple negative breast cancers. Being the core spliceosome associated proteins, SNRPD1 and SNRPE have been both proposed as therapeutic targets for breast cancer management. Yet, their differences regarding their prognostic and therapeutic use as well as roles during carcinogenesis are largely unreported.
We conducted in silico analysis at gene expression and genetic levels to differentiate the clinical relevance of SNRPD1 and SNRPE, and explored their differential functionalities and molecular mechanistic associations with cancer in vitro.
We showed that high SNRPD1 gene expression was prognostic of poor breast cancer survival whereas SNRPE was not. The SNRPD1 expression quantitative trait loci, rs6733100, was found independently prognostic of breast cancer survival using TCGA data. Silencing either SNRPD1 or SNRPE independently suppressed the growth of breast cancer cells, but decreased migration was only observed in SNRPD1-silenced cells. Knocking down SNRPD1 but not SNRPE triggers doxorubicin resistance in triple negative breast cancer cells. Gene enrichment and network analyses revealed the dynamic regulatory role of SNRPD1 on cell cycle and genome stability, and the preventive role of SNRPE against cancer stemness that may neutralize its promotive role on cancer cell proliferation.
Our results differentiated the functionalities of SNRPD1 and SNRPE at both prognostic and therapeutic levels, and preliminarily explained the driving mechanism that requires additional explorations and validations.