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Multiple myeloma (MM) is a common severe hematopoietic malignancy occuring in aged population. MicroRNA (miR)-497 was previously reported to contribute to the apoptosis of other cell types, presumably through targeting B-cell lymphoma 2 (Bcl-2). In the present study, miRNA and protein expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The cell proliferation and viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and plate clonality assays, and the cell growth cycle was measured with a flow cytometer. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling, Annexin V and caspase-3 activity assays were performed to examine the cell apoptotic rates. The results showed that miR-497 was markedly decreased, whereas Bcl-2 was enhanced in MM tissues and cell lines. miR-497 targeted Bcl-2 and affected its downstream apoptosis-related genes. The overexpression of miR-497 promoted MM cell apoptosis through cell cycle arrest, and decreased colony genesis ability and viability. In addition, miR-497 increased the sensitivity of MM cells to bortezomib. Taken together, miR-497 suppressed MM cell proliferation and promoted apoptosis by directly targeting Bcl-2 and altering the expression of downstream apoptosis-related proteins. The combination of miR-497 and bortezomib may enhance drug sensitivity, serving as a potentially available therapeutic method for MM.

Background: Circular RNAs (circRNAs) crucially regulate tumor progression. In this study, we examined the functional roles and mechanisms of hsa_circ_0003489 in multiple myeloma (MM).Methods: Upon altering the expressions of hsa_circ_0003489, miR-874-3p, and/or histone deacetylase 1 (HDAC1) in MM1.R cells and treating them with bortezomib (BTZ), cell viability was examined by CCK-8 assay; cell proliferation by Ki-67 immunofluorescence; apoptosis by TUNEL staining, flow cytometry, and western blot; and autophagy by electron microscopy and western blot. The interaction between hsa_circ_0003489 and miR-874-3p as well as that between miR-874-3p and HDAC1 was examined by expressional analysis, dual luciferase reporter assay, and RNA immunoprecipitation. The in vivo impacts of hsa_circ_0003489 on MM growth and sensitivity to BTZ were examined using an MM xenograft mouse model.Results: Knocking down hsa_circ_0003489 significantly inhibited the viability, cell proliferation, and autophagy, while promoting the apoptosis of MM cells in vitro and MM xenograft in vivo. Suppressing hsa_circ_0003489 also further boosted the cytotoxic effects of BTZ in MM cells and reversed its promoting effect on autophagy.Mechanically, hsa_circ_0003489 acted as a sponge of miR-874-3p and positively regulated the expression of miR-874-3p target, HDAC1. MiR-874-3p and HDAC1 essentially mediated the effects of hsa_circ_0003489 on cell viability, proliferation, apoptosis, and autophagy. Conclusion:The hsa_circ_0003489/miR-874-3p/HDAC1 axis critically regulates the balance between apoptosis and autophagy. Silencing hsa_circ_0003489 sensitizes MM cells to BTZ by inhibiting autophagy and thus may boost the therapeutic effects of BTZ.

Chloramphenicol is an old antibiotic that also inhibits mammalian mitochondrial protein synthesis. Our studies demonstrated that chloramphenicol is highly cytotoxic to myeloma cells, acting in a dose- and time-dependent manner. Chloramphenicol sharply suppressed ATP levels in myeloma cells at concentrations ≥ 25 μg/mL. Colorimetric and clonogenic assays indicate that chloramphenicol inhibits growth of myeloma cell lines at concentrations ≥ 50 μg/mL, and inhibits primary myeloma cell growth at concentrations ≥ 25 μg/mL. Flow cytometry and Western blotting showed that chloramphenicol induces myeloma cell apoptosis at concentrations ≥ 50 μg/mL. Chloramphenicol increased levels of cytochrome c, cleaved caspase-9 and cleaved caspase-3, suggesting that myeloma cell apoptosis occurs through the mitochondria-mediated apoptosis pathway. It thus appears chloramphenicol is not only an old antibiotic, it is also a potential cytotoxic agent effective against myeloma cells. This suggests chloramphenicol may be an effective “new” drug for the treatment of myeloma.

Background: Pelvic lymph nodes metastasis is an important prognostic factor for patients with cervical carcinoma. However, the relationships between the number of positive nodes, site of metastases nodes, adjuvant therapy and the prognosis is controversial. The purpose of this study was to investigate the influence of positive lymph nodes on the prognosis of Chinese women with stage IB1-IIB cervical carcinoma.