Targeting lncRNA RP11-358L4.1 attenuates breast cancer cell proliferation and is associated with cell cycle and immune-related transcriptomic signatures.

BACKGROUND

Breast cancer (BC) is a leading cause of morbidity and mortality in women, with metastasis and recurrence being major determinants of poor prognosis. Long non-coding RNAs (lncRNAs) have emerged as important regulators in cancer biology, but the role of RP11-358L4.1 in BC progression and chemotherapeutic response remains unclear.

METHODS

RP11-358L4.1 expression was measured in 25 paired BC and adjacent normal tissues. Functional assays following RP11-358L4.1 knockdown in MCF-7 and BT-474 cells assessed proliferation, apoptosis, migration, and carboplatin sensitivity. Expression of cell cycle regulators CDK1, CDK2, and p21 was evaluated. Transcriptomic sequencing, integrated with GEO datasets, was used to identify downstream targets, followed by gene set enrichment and immune infiltration analyses. Kaplan-Meier survival analysis determined prognostic relevance.

RESULTS

RP11-358L4.1 was upregulated in breast cancer tissues and cell lines. RP11-358L4.1 knockdown suppressed proliferation and migration, increased apoptosis, and induced G0/G1 arrest in MCF-7 and BT-474 cells. RNA-seq and integrated transcriptomic analyses nominated CXCL11 and KLF2 as candidate genes associated with RP11-358L4.1-related transcriptional patterns, with enrichment results suggesting immune- and cell-cycle-related signatures. Immune-cell deconvolution further suggested differences in estimated immune infiltration across groups. In survival analyses, higher CXCL11 expression was associated with worse distant metastasis-free survival and showed a trend toward poorer overall survival, whereas higher KLF2 expression was associated with better outcomes.

CONCLUSION

RP11-358L4.1 is associated with aggressive cellular phenotypes and platinum response in vitro. CXCL11 and KLF2 represent candidate correlates linked to RP11-358L4.1 associated transcriptional signatures, providing testable hypotheses for future mechanistic and clinical validation.