bims-netuvo 2021-09-19 papers

Issue of 2021‒09‒19
three papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Prostate. 2021 Sep 17.

SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence.

Silvia Hernández-Llodrà, Laura Segalés, Nuria Juanpere, Tech Marta Lorenzo, Marta Salido, Lara Nonell, Tech David López, Alejo Rodríguez-Vida, Joaquim Bellmunt, Lluís Fumadó, Lluís Cecchini, Josep Lloreta-Trull.

BACKGROUND: In the non-ETS fusion of prostate cancer (PCa) pathway, SPOP mutations emerge as a distinct oncogenic driver subclass. Both SPOP downregulation and mutation can lead to SPOP target stabilization promoting dysregulation of key regulatory pathways. CHD1 gene is commonly deleted in PCa. CHD1 loss significantly co-occurs with SPOP mutations, resulting in a PCa subclass with increased AR transcriptional activity and with a specific epigenetic pattern.METHODS: In this study, SPOP alterations at mutational and protein levels and CHD1 copy number alterations have been analyzed and correlated with ERG and PTEN protein expression and with the clinical pathological features of the patients.
RESULTS: SPOP protein loss has been detected in 42.9% of the cases, and it has been strongly associated with PTEN protein loss (p < .001). CHD1 gene loss has been detected in 24.5% and SPOP mutations in 5.9% of the cases. Loss of CHD1 has been strongly associated with SPOP mutations (p = .003) and has shown a trend to be associated with ERG wt cancers (p = .08). The loss of SPOP protein (p = .01) and the combination of PTEN and SPOP protein loss (p = .002) were both statistically more common in grade group 5 cancers, with a prevalence of 60% and 37.5%, respectively. Furthermore, SPOP loss/PTEN loss and SPOP wt/PTEN loss phenotypes were strongly associated with extraprostatic perineural infiltration (p = .007). Strong CHD1 loss was associated with a shorter time to PSA recurrence in the univariate (p = .04), and showed a trend to be associated with the PSA recurrence risk in the multivariate analysis (p = .058).
CONCLUSIONS: The results of the present study suggest that the loss of SPOP protein expression, either alone or in combination with loss of PTEN and, on the other hand, a marked loss of the CHD1 gene are very promising prognostic biomarkers in PCa.

Keywords: CHD1; PSA recurrence; PTEN; SPOP; prostate cancer

DOI: https://doi.org/10.1002/pros.24218

Exp Mol Pathol. 2021 Sep 09. pii: S0014-4800(21)00082-4. [Epub ahead of print] 104682

miR-876-3p suppresses the progression of colon cancer and correlates the prognosis of patients.

Huili Ma, Mintao Li, Zhuting Jia, Xi Chen, Naitong Bu.

BACKGROUND: miR-876-3p has been identified to be downregulated in colon cancer, implying the potential biological function in the progression and prognosis of colon cancer. The clinical significance and the biological function of miR-876-3p were investigated in this study to assess the potential of miR-876-3p in acting as a novel biomarker of the progression of colon cancer.METHODS: The expression of miR-876-3p in colon cancer was evaluated by RT-qPCR. The clinical significance of miR-876-3p was assessed by associated its expression level with the clinical features and prognosis of patients. The biological function of miR-876-3p was estimated by the CCK8 and Transwell assay in vitro.
RESULTS: The significant downregulation of miR-876-3p was observed in colon cancer tissues and cells, which was closely associated with the lymph node metastasis status, TNM stage, and the perineural invasion of patients. miR-876-3p served as an independent indicator that was negatively associated with the prognosis of patients. In colon cancer cells, miR-876-3p showed significant inhibitory effects on the proliferation, migration, and invasion, indicating its tumor suppressor role in the progression of colon cancer.
CONCLUSION: miR-876-3p might be involved in colon cancer development, which provides a potential therapeutic target for colon cancer treatment.

Keywords: Colon cancer; Development; Prognosis; miR-876-3p

DOI: https://doi.org/10.1016/j.yexmp.2021.104682

Elife. 2021 Sep 16. pii: e67535. [Epub ahead of print]10

Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice.

Susu Pan, Kaili Yin, Zhiwei Tang, Shuren Wang, Zhuo Chen, Yirong Wang, Hongxia Zhu, Yunyun Han, Mei Liu, Man Jiang, Ningzhi Xu, Guo Zhang.

Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of β2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, eg. celastrol, might be a novel strategy for colorectal cancer treatment.

Keywords: cancer biology; mouse; neuroscience

DOI: https://doi.org/10.7554/eLife.67535