In most cancers, tumor hypoxia downregulates the expression of C‐C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is yet not clear. We compared non‐cancerous and lung‐adenocarcinoma human samples for hypoxia‐inducible factor 1‐alpha (HIF‐1A), microRNA‐210‐3p (mir‐210‐3p) and CCL2 levels. Mechanistic studies were performed on lung adenocarcinoma cell lines and 3D tumor spheroids to understand the role of hypoxia‐induced miR‐210‐3p in the regulation of CCL2 expression and macrophage polarization. HIF‐1 A stabilization increases miR‐210‐3p levels in lung adenocarcinoma and impairs monocyte infiltration by inhibiting CCL2 expression. Mechanistically, miR‐210‐3p directly binds to the 3'untranslated region (UTR) of CCL2 mRNA and silences it. Suppressing miR‐210‐3p substantially downregulates the effect of hypoxia on CCL2 expression. Monocyte migration is significantly hampered in miR‐210‐3p mimic‐transfected HIF‐1A silenced cancer cells. In contrast, inhibition of miR‐210‐3p in HIF‐1A‐overexpressed cells markedly restored monocyte migration, highlighting a direct link between miR‐210‐3p level and tumor monocyte burden. Moreover, miR‐210‐3p inhibition in 3D tumor spheroids promotes monocyte recruitment and skewing towards an anti‐tumor M1 phenotype. Anti‐hsa‐miR‐210‐3p‐locked nucleic acid (LNA) delivery in a lung tumor xenograft zebrafish model caused tumor regression, suggesting that miR‐210‐3p could be a promising target for immunomodulatory therapeutic strategies against lung adenocarcinoma.
Butterflies have always attracted attention due to their unique colourations. As most butterflies are highly specific in their niche utilisation, abundance of the species in a locality may advocate status of ecosystem functioning and environmental health. In recent times, different anthropogenic activities and unscientific management of nature have resulted in a decline of butterfly communities at a rapid rate. The objective of the present study is to study butterfly diversity in and around Midnapore Town, West Bengal, India. A total of 82 butterfly species belonging to six families were recorded during the two years of the study period. Of the six families Nymphalidae is the most abundant family comprising 42.54% of the total population followed by Lycaenidae (22.5%), Pieridae (19.03%), Papilionidae (8.58%), Hesperiidae (7.24%), and Riodinidae (0.11%). Different diversity indices, Lorenz curve, Whittaker plot, and Gini index show high diversity in the butterfly community structure. As Midnapore Town is the connecting area between the plains of Bengal and Chota Nagpur Plateau, the present study may be the baseline for further ecological, environmental, and conservation studies.
Under the condition of chronic obesity, an increased level of free fatty acids along with low oxygen tension in the adipose tissue creates a pathophysiological adipose tissue microenvironment (ATenv) leading to the impairment of adipocyte function and insulin resistance. Here, we found the synergistic effect of hypoxia and lipid (HL) surge in fostering adipose tissue macrophages(ATMs) inflammation and its polarization. ATenv significantly increased miR-210-3p expression in ATMs which promotes NF-ĸB activation-dependent proinflammatory cytokines expressions along with the downregulation of anti-inflammatory cytokines expression. Interestingly, delivery of miR-210-3p mimic significantly increased the macrophage inflammation in absence of HL co-stimulation; while miR-210-3p inhibitor notably compromised HL-induced macrophage inflammation through increased production of SOCS1 (suppressor of cytokine signalling 1), a negative regulator of NF-ĸB inflammatory signalling pathway. Mechanistically, miR-210 directly binds to 3' UTR of SOCS1 mRNA and silenced its expression and thus preventing proteasomal degradation of NF-ĸB p65. Direct delivery of anti-miR-210-3p LNA in the ATenv markedly rescued mice from obesity-induced adipose tissue inflammation and insulin resistance. Thus, miR-210-3p inhibition in ATMs could serve as a novel therapeutic strategy for managing obesity-induced type 2 diabetes.
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