MIR99B (MicroRNA 99b)

Together, these findings identify the SPACA6-hosted miR-99b~125a~let-7e cluster as a regulator of BRAF/MEK inhibitor resistance through promotion of tumor survival and of an immunosuppressive microenvironment. Targeting this miRNA cluster may provide novel therapeutic opportunities to overcome drug resistance in metastatic melanoma.

Shikonin induces apoptosis in renal cancer cells by modulating the MAPK/ERK pathway and through cell-line-specific, cell-type-dependent regulation of miR-15b, miR-99b, and miR-181a. These findings highlight the importance of cell-type-dependent miRNA regulation and underscore the therapeutic potential of shikonin in ccRCC.

Findings from GC cells, organoids and PDX models demonstrated that overexpression of the miR-99b cluster sensitized GC to cisplatin, likely through its inhibitory effects on mitochondrial respiratory function, particularly OXPHOS...Moreover, elevated KMT5A expression and decreased miR-125a-5p expression indicated both poorer prognosis and chemo-resistance in patients with GC. This study highlights the multifaceted roles of the miR-99b cluster in GC and offers novel perspectives for the development of innovative therapeutics aimed at overcoming chemoresistance and enhancing treatment efficacy for GC patients.

A prominent example is miR-99b, which overlaps the 5' splice junction of the poorly characterized long non-coding RNA (lncRNA) sperm acrosome-associated 6 antisense RNA1 (SPACA6-AS1) and, through base pairing, enhances SPACA6-AS1 pre-mRNA levels. These results highlight the diverse and context-dependent functions of nuclear miRNAs in gene regulation and cancer progression, broadening our understanding of their regulatory potential beyond the cytoplasm.

Additionally, miRNA expression patterns in NAT may indicate a predisposition to tumor recurrence. The study concludes that miRNA dysregulation in non-neoplastic gastric mucosa suggests these tissues may be cancer-prone environments.

A total of 29 patients with lung adenocarcinoma who received pembrolizumab combined with pemetrexed and carboplatin were enrolled. These findings were further confirmed by clinical imaging. sEV miRNAs derived from patients with lung cancer showed promise for identifying true responders to combined immunochemotherapy.

We review the recent research on this family, summarize its implications in cancer, and explore its potential as a biomarker and cancer therapeutic target. This review contributes to the clinical translation of the miR-99 family members.

The interaction between ER and HER family receptors, particularly HER2 and epidermal growth factor receptor (EGFR), drives resistance to standard therapies such as tamoxifen and trastuzumab by activating key signaling pathways, including PI3K/AKT and RAS/MAPK. Targeting miR-99b-5p could represent a potential therapeutic strategy to improve treatment outcomes in ER+/HER2+ breast cancer. Further research is needed to clarify the underlying molecular mechanisms and validate the therapeutic potential of miR-99b-5p inhibition in clinical applications.

[This retracts the article on p. 114 in vol. 14, PMID: 38323281.].

Receiver operating characteristic (ROC) curve analysis indicated that mir-222 identified GC patients with a maximum area under the curve (0.73, 95% confidence interval 0.57-0.89). Plasma mir-222 was confirmed to be dysregulated in patients with GC, irrespective of blood biochemical parameters.

The present study shows that drug-resistant cell exosomes miR-99b-3p can directly influence the migration, proliferation, and paclitaxel sensitivity of sensitive cells via PPP2CA. Additionally, the exosomes from drug-resistant cells can influence the polarization of macrophage M2 in the tumor microenvironment, which can also have an impact on the proliferation, migration, and paclitaxel sensitivity of sensitive cells.

Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.