Oncology reports
-
Muscle atrophy F-Box (MAFbx)/atrogin-1 and muscle ring-finger-1 (MuRF-1) have been identified as two muscle-specific E3 ubiquitin ligases that are highly expressed in skeletal muscle during muscle atrophy. However, the role of muscle-specific E3 ubiquitin ligases during the process of muscle atrophy of cancer cachexia remains largely unknown. In the present study, we analyzed the expression of atrogin-1 and MuRF-1 in the skeletal muscle of patients with malignant and benign disease. ⋯ Significant myotube atrophy with atrogin-1 overexpression was observed in the C2C12 cells treated with TNF-α. Meanwhile, knockdown of atrogin-1 by small interfering RNA (siRNA) protected C2C12 cells from the adverse effect of TNF-α. In conclusion, muscle-specific E3 ubiquitin ligases were upregulated during cancer cachexia, and atrogin-1 may be a potential molecular target for treating muscle atrophy induced by cancer cachexia.
-
Male breast cancer (MBC) is a rare disease, accounting for ~1% of all breast cancer cases worldwide. Although other genes are also involved, predisposing genetic factors to MBC include germline mutations in the BRCA genes (BRCA2). Among the other genes, partner and localizer of BRCA2 (PALB2) is considered a moderate-penetrance breast cancer susceptibility gene that may also play a role in MBC predisposition. ⋯ This novel mutation was named c.1285_1286delAinsTC (p. I429SfsX12) and is localized in exon 4 of PALB2, in the region encoding for the ChAM motif which is important for the efficient association of PALB2 to chromatin and for recruitment of the BRCA complex to accumulate RAD51 at double-strand break sites. Our findings indicate that PALB2 could be added to the list of breast cancer susceptibility genes also in families with MBC cases.
-
Primary and metastatic cancers that affect bones are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In the present study, we investigated whether inhibition of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to the development of bone cancer pain via sensitization of dorsal horn wide dynamic range (WDR) neurons. ⋯ Furthermore, we discovered that blockade of KCNQ/M channels in the spinal cord by local administration of XE-991, a specific KCNQ/M channel blocker, caused a robust increase in excitability of dorsal horn WDR neurons, while, producing obvious pain hypersensitivity in normal rats. On the contrary, activation of spinal KCNQ/M channels by retigabine, a selective KCNQ/M channel opener, not only inhibited the bone cancer‑induced hyperexcitability of dorsal horn WDR neurons, but also alleviated mechanical allodynia and thermal hyperalgesia in the bone cancer rats, while all of these effects of retigabine could be blocked by KCNQ/M-channel antagonist XE-991. All things considered, these results suggest that suppression of KCNQ/M channels in the spinal cord likely contributes to the development of bone cancer pain via sensitization of dorsal horn WDR neurons in rats following tumor cell inoculation.
-
Previous studies have shown that Dickkopf‑3 (Dkk3) is inactivated in lung cancer cells, while the inactivation of the Wnt/β‑catenin signaling pathway by Dkk3 inhibits lung cancer progression. In the present study, we investigated whether Dkk3 enhances the sensitivity of lung cancer cells to cisplatin. A549, Calu1 and H460 lung adenocarcinoma cell lines were transfected with DKK3 siRNA, while the cisplatin‑resistant subline A549cis was transfected with DKK3. ⋯ Moreover, tumor growth was retarded more in cisplatin‑treated nude mice seeded with A549cis‑DKK3 cells than with A549cis cells. Cell viability increased with the pretreatment of SB216763 for 2 h in A549cis and A549cis‑DKK3 cells incubated with cisplatin (1 µM) for 72 h. In conclusion, the re‑activation of Dkk3 enhances the chemosensitivity to cisplatin in cisplatin‑resistant lung adenocarcinoma cell lines, which requires additional studies to realize this potential in clinical use.
-
Human aspartyl-(asparaginyl)-β-hydroxylase (HAAH) is a type 2 transmembrane protein and an α-ketoglutarate-dependent dioxygenase that can stereospecifically catalyze the post-translational hydroxylation reaction of β-carbon atoms of aspartic acid and asparagine residues present in epidermal growth factor-like domains of certain specific proteins. Humbug is a truncated isoform of aspartyl (asparaginyl) β-hydroxylase that lacks the catalytic domain. A series of reports demonstrated that overexpression of HAAH/humbug was identified in hepatocellular carcinoma (HCC) and various tumor tissues. ⋯ No statistically significant difference was observed for these two factors. HAAH/humbug expression levels were upregulated in almost all the HCC tissues when compared to the adjacent cancer-free tissue, irrespective of the cut‑off point used. Results of the present study suggested that HAAH/humbug is a potential diagnostic and prognostic biomarker for the treatment of HCC.