Chemoresistance remains the uppermost disincentive for cancer treatment on account of many genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) are emerging players in promoting cancer initiation and progression. However, the regulation and function in chemoresistance are largely unknown. Herein, we identified ARHGAP5-AS1 as a lncRNA upregulated in chemoresistant gastric cancer cells and its knockdown reversed chemoresistance. Meanwhile, high ARHGAP5-AS1 expression was associated with poor prognosis of gastric cancer patients. Intriguingly, its abundance is affected by autophagy and SQSTM1 is responsible for transporting ARHGAP5-AS1 to autophagosomes. Inhibition of autophagy in chemoresistant cells, thus, resulted in the upregulation of ARHGAP5-AS1. In turn, it activated the transcription of ARHGAP5 in the nucleus by directly interacting with ARHGAP5 promoter. Interestingly, ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m 6 A modification of ARHGAP5 mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. In summary, impaired autophagic degradation of lncRNA ARHGAP5-AS1 in chemoresistant cancer cells promoted chemoresistance. It can activate the transcription of ARHGAP5 in the nucleus and stimulate m 6 A modification of ARHGAP5 mRNA to stabilize ARHGAP5 mRNA in the cytoplasm by recruiting METTL3. Therefore, targeting ARHGAP5-AS1/ARHGAP5 axis might be a promising strategy to overcome chemoresistance in gastric cancer.

The growing understanding of RNA functions and their crucial roles in diseases promotes the application of various RNAs to selectively function on hitherto “undruggable” proteins, transcripts and genes, thus potentially broadening the therapeutic targets. Several RNA-based medications have been approved for clinical use, while others are still under investigation or preclinical trials. Various techniques have been explored to promote RNA intracellular trafficking and metabolic stability, despite significant challenges in developing RNA-based therapeutics. In this review, the mechanisms of action, challenges, solutions, and clinical application of RNA-based therapeutics have been comprehensively summarized.

Propargylic alcohols and their derivatives are important classes of organic compounds that can be easily accessible from terminal alkynes and aldehydes or ketones. They are attractive and have been extensively applied as synthetic intermediates in modern organic synthesis. Recent investigations on the chemistry of propargylic alcohols and their derivatives disclosed a variety of highly efficient Lewis acid-catalyzed cascade reactions based on Meyer−Schuster rearrangement of propargylic alcohols and [3,3] rearrangement of propargylic esters and propargyl vinyl ethers. A tremendous number of structurally versatile enones, carbocycles, and heterocycles have been constructed through these methodologies. These advances, including our recent researches in this field, are summarized in this review.