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Simple Summary: Lung adenocarcinoma, the most prevalent type of lung cancer, presents a significant treatment challenge owing to drug resistance. This study aimed to investigate the role of long non-coding RNAs (lncRNAs) in promoting intrinsic resistance in three lung adenocarcinoma cell lines from the onset of treatment. Drug-tolerant persister (DTP) cells, a subset of cancer cells with the ability to survive and proliferate after exposure to therapeutic drugs, were generated. RNA sequencing was used to investigate the differential expression of lncRNAs, and the clinical relevance of lncRNAs was assessed in a cohort of lung adenocarcinoma patients from The Cancer Genome Atlas. Knockdown of these lncRNAs increases the sensitivity of the analyzed cell lines to therapeutic drugs. This study provides an opportunity to investigate the role of lncRNAs in the genetic and epigenetic mechanisms underlying intrinsic resistance. Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance poses a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister (DTP) cells are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study in cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after single exposure to tyrosine kinase inhibitors (TKIs; erlotinib or osimertinib). After establishing DTP cells, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT–qPCR validated the overexpression of lncRNAs and mRNA in the residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms that underlie intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival (OS) of patients with lung cancer. [ABSTRACT FROM AUTHOR]

Objective: Autosomal dominant (AD) inheritance accounts for 15–20% of retinitis pigmentosa (RP) familial cases. The characterization of AD RP-related mutations remains essential because it provides both accurate diagnosis and clinically important prognostic information. Rhodopsin ( RHO) and peripherin/RDS are the two most common mutated genes in AD RP in several series. However, the genetic characterization of patients from distinct ethnic groups will help to define the relative contribution of particular AD RP-related genes. In the present study, a search for causal mutations in RHO and peripherin/RDS in a group of 28 Mexican RP probands with AD inheritance was performed. Methods: Methods included complete ophthalmologic examination as well as fluorangiographic and electroretinographic assessment. Molecular analysis included Polymerase (PCR) amplification and direct nucleotide sequencing of the coding exons of RHO and peripherin/RDS in DNA from affected subjects. Mutation-carrying exons were analyzed in a total of 29 first-degree relatives from some of these families. Results: Five RHO mutations, including two novel ones and three previously reported, were demonstrated in this RP sample. Novel mutations were c.365A>G in exon 2 (Glu122Gly), and c.233A> in exon 1 (Asn78Ile). The other three RHO mutations were Phe45Leu, Arg135Trp, and Ser186Trp. No peripherin/RDS gene mutations were demonstrated in the remaining 23 probands. Conclusion: Our study adds to the mutational spectrum of adRP by identifying two novel RHO mutations. RHO mutations were responsible of 17% of AD RP Mexican cases, a figure slightly lower to that found in other ethnic groups. Peripherin/RDS mutations are apparently an uncommon cause of AD RP in this population. [ABSTRACT FROM AUTHOR]