LncRNA XIST promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by downregulating miR-27b-3p.

Chemotherapy resistance has become a major obstacle to effective treatment of human cancer. This study aimed to investigate the effect of lncRNA XIST on cell proliferation and cisplatin (CDDP) of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blot analysis were used to detect mRNA and protein expression. CCK-8 and flow cytometry assays were explored to evaluate CDDP sensitivity in OSCC cells. The relationship between lncRNA XIST and miR-27b-3p was confirmed by luciferase reporter assay. The results showed that lncRNA XIST was upregulated in OSCC tissues, cell lines, and CDDP-resistant OSCC cells. Functionally, upregulation of lncRNA XIST promoted cell proliferation, enhanced CDDP resistance, and inhibited apoptosis in OSCC cells. In addition, lncRNA XIST acts as a molecular sponge for miR-27b-3p in OSCC. Downregulation of miR-27b-3p partially reversed the tumor suppression effect and CDDP chemosensitivity of XIST knockdown in CDDP-resistant OSCC cells. In conclusion, lncRNA XIST promotes cell proliferation and enhances resistance to CDDP in OSCC by downregulating miR-27b-3p.

Ma SQ ，Wang YC ，Li Y ，Li XY ，Yang J ，Sheng YM ... -  《JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS》

LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR-184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR-184 to repress its expression. Rescue experiments suggested that downregulation of miR-184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP-resistant OSCC cells. Moreover, UCA1 could perform as a miR-184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP-mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients.

Fang Z ，Zhao J ，Xie W ，Sun Q ，Wang H ，Qiao B ... -  《Cancer Medicine》

LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression.

Wang X ，Li H ，Shi J 《-》

Upregulation of Long Noncoding RNA (lncRNA) X-Inactive Specific Transcript (XIST) is Associated with Cisplatin Resistance in Non-Small Cell Lung Cancer (NSCLC) by Downregulating MicroRNA-144-3p.

Tian LJ ，Wu YP ，Wang D ，Zhou ZH ，Xue SB ，Zhang DY ，Wei YG ，Liu W ... -  《MEDICAL SCIENCE MONITOR》

LncRNA XIST Contributes to Cisplatin Resistance of Lung Cancer Cells by Promoting Cellular Glycolysis through Sponging miR-101-3p.

Non-small-cell lung carcinoma is one of the most frequently diagnosed cancers. Cisplatin (CDDP) is a currently applied standard anticancer agent for advanced lung cancers. Although effectively clinical response was achieved initially, a large fraction of lung cancer patients developed cisplatin resistance. Therefore, understanding the molecular mechanisms of chemoresistance is crucial for anti-lung cancer therapy. Long non-coding RNA (lncRNA)-X-inactive-specific transcript (XIST) has been reported to be positively associated with multiple cancers. Currently, the precise role and mechanism of XIST in cisplatin resistance of lung cancer have not been elucidated. The expression levels of miR-101-3p and lncRNA XIST were detected by qRT-PCR. Cisplatin-resistant lung cancer cell line was established by selecting the survival cells under gradually increased cisplatin treatments. The cell proliferation was detected by MTT assay, and the cellular glucose metabolism rate was evaluated by Seahorse metabolic flux analysis and glucose uptake and lactate product assays. Glycolysis-related protein expression levels were detected by Western blot. Dual luciferase reporter was constructed to determine the lncRNA-miRNA interaction. Here, we report XIST is significantly upregulated in lung cancer tissues compared with normal lung tissues. In addition, cisplatin-resistant lung cancer cells displayed remarkably elevated XIST expression. We demonstrated that miR-101-3p functioned as a tumor suppressor in lung cancer and sensitized lung cancer cells to cisplatin. Bioinformatics analysis predicted miR-101-3p could be a potential target of XIST through direct binding with it as a competing endogenous RNA, which was further validated from lung tumor tissues and cell lines by luciferase assay. Intriguingly, XIST significantly promoted cellular glycolysis rate of lung cancer cells. The extracellular acidification rate, glucose uptake, and lactate product were elevated by XIST overexpression. On the contrary, miR-101-3p effectively suppressed glycolysis rate. Finally, we demonstrated silencing XIST significantly recovered miR-101-3p expression and downregulated expression of glycolysis key enzymes, a phenotype could be further overridden by miR-101-3p inhibition. This study reveals a new molecular mechanism for the lncRNA-XIST-promoted cisplatin resistance via sponging miR-101-3p, leading to de-repression of cellular glycolysis. Moreover, these findings warrant further in vivo investigations to study XIST as a potential target to overcome cisplatin resistance.

Hua G ，Zeng ZL ，Shi YT ，Chen W ，He LF ，Zhao GF ... -  《-》