Long noncoding RNA TINCR facilitates hepatocellular carcinoma progression and dampens chemosensitivity to oxaliplatin by regulating the miR-195-3p/ST6GAL1/NF-κB pathway

Abstract

Background Long non-coding RNAs (lncRNA) have an essential role in progression and chemoresistance of hepatocellular carcinoma (HCC). In-depth study of specific regulatory mechanisms is of great value in providing potential therapeutic targets. The present study aimed to explore the regulatory functions and mechanisms of lncRNA TINCR in HCC progression and oxaliplatin response. Methods The expression of TINCR in HCC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration, invasion, and chemosensitivity were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and apoptosis assays. Luciferase reporter assays and RNA pulldown were used to identify the interaction between TINCR and ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) via miR-195-3p. The corresponding functions were verified in the complementation test and in vivo animal experiment. Results TINCR was upregulated in HCC and associated with poor patient prognosis. Silencing TINCR inhibited HCC proliferation, migration, invasion, and oxaliplatin resistance while overexpressing TINCR showed opposite above-mentioned functions. Mechanistically, TINCR acted as a competing endogenous (ceRNA) to sponge miR-195-3p, relieving its repression on ST6GAL1, and activated nuclear factor kappa B (NF-κB) signaling. The mouse xenograft experiment further verified that knockdown TINCR attenuated tumor progression and oxaliplatin resistance in vivo. Conclusions Our finding indicated that there existed a TINCR/miR-195-3p/ST6GAL1/NF-κB signaling regulatory axis that regulated tumor progression and oxaliplatin resistance, which might be exploited for anticancer therapy in HCC.

Hypoxic trophoblasts secreted exosomes promote autophagy through TINCR to impair angiogenesis and drive preeclampsia

“…Sharing the same miRNA response elements as their cognate genes, lncRNAs could serve as ceRNAs. For instance, a study revealed that TINCR acts as a sponge for miR-195-3p and promotes hepatocellular carcinoma progression [41] . According to bioinformatics analysis, TINCR possessed potential binding sites for miR-424-5p and miR-424-5p could target the 3'UTR of ATG5 mRNA.…”

Extracellular vesicles improve GABAergic transmission in Huntington’s disease iPSC-derived neurons

“…Our data from CTRs-EVs supports the upregulation of some particular miRNAs with previously validated targets that modulate GABAergic synapses (eg. miR-19a-3p, miR-211, miR-1180-3p, miR-941) (Arcila et al, 2014;Bernreuther et al, 2006;Chen et al, 2022;Hu et al, 2012;Jovasevic and Radulovic, 2021;Li et al, 2009;Luo et al, 2016;Mei et al, 2022;O'Connor et al, 1992;Wang et al, 2021;Xiao et al, 2015;Xu et al, 2019;2018a;Zou et al, 2016) (Table 2). Interestingly, the cysteine string protein, encoded by the DNAJC5 gene, resides in presynaptic terminals, clathrin-coated vesicles and neuroendocrine secretory granules and is involved in neurotransmitter release and most importantly has been linked to Huntington's and Parkinson's diseases (Chandra et al, 2005;Miller et al, 2003;Ruiz et al, 2008).…”

Protein glycosylation alterations in hepatocellular carcinoma: function and clinical implications

“…Moreover, microRNA and lncRNA also regulate sialylation in HCC. Long noncoding RNA TINCR acted as a competing endogenous (ceRNA) to sponge miR-195-3p, thereby protecting ST6GAL1 from miR-195-3p-induced repression; subsequently, elevated ST6GAL1 promoted HCC progression and chemoresistance [ 50 ]. In addition, miR-26a, miR-548l, and miR-34a have been reported to inhibit the expression of ST3GAL5, which encodes Lactosylceramide alpha-2,3-sialyltransferase, to suppress HCC cell proliferation and migration [ 51 ].…”