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Overcoming drug resistance of cancer cells is the major challenge in molecular oncology. Here, we demonstrate that long non-coding RNA LINC00973 is up-regulated in normal and cancer cells of different origins upon treatment with different chemotherapeutics. Bioinformatics analysis shows that this is a consequence of DNA damage response pathway activation or mitotic arrest. Knockdown of LINC0973 decreases p21 levels, activates cellular proliferation of cancer cells, and suppresses apoptosis of drug-treated cells. We have found that LINC00973 strongly increases p21 protein content, possibly by blocking its degradation. Besides, we have found that ectopic over-expression of LINC00973 inhibits formation of the pro-survival p53-Ser15-P isoform, which preserves chromosome integrity. These results might open a new approach to the development of more efficient anti-cancer drugs.

Using RNA-seq, RT-qPCR, and bioinformatics we have studied the influence of a wide spectrum of chemotherapeutic drugs on transcription of AKR1B10 , AKR1C1 , ALDH1A1 , and ALDH1A3 genes, which encode the major aldehyde-metabolizing enzymes. The strongest alterations were detected in case of AKR1B10 mRNA that was significantly upregulated in wild type p53 cancer cells, but downregulated in mutant p53 cancer cells. Subsequent experiments demonstrated the significant and consistent decrease in the AKR1B10 mRNA content in sera of colon cancer patients, as compared to sera of healthy donors (p<0.0001, SPE=92.9%, SNE=79.3%, AUC=0.889), which implies that this RNA is a valuable marker for serological diagnosis of colorectal cancer. Moreover, we have found that ALDH1A3 protein is a key inactivator of ROS-generated aldehydes, which is a perspective target for the development of new chemotherapeutic drugs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Early prediction of tumor relapse depends on the identification of new prognostic cancer biomarkers, which are suitable for monitoring tumor response to different chemotherapeutic drugs. Using RNA-Seq, RT-qPCR, bioinformatics, and studies utilizing the murine tumor xenograft model, we have found significant and consistent changes in the abundance of five lincRNAs (LINC00973, LINC00941, CASC19, CCAT1, and BCAR4) upon treatment of both HT-29 and HCT-116 cells with 5-fluorouracil, oxaliplatin, and irinotecan at different doses and durations; both in vitro and in vivo. The most frequent changes were detected for LINC00973, whose content is most strongly and consistently increased upon treatment of both colon cancer cell lines with all three chemotherapeutic drugs. Additional studies are required in order to determine the molecular mechanisms by which anticancer drugs affect LINC00973 expression and to define the consequences of its upregulation on drug resistance of cancer cells., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Using real-time RT-PCR in combination with bioinformatics, we have shown for the first time that the treatment of HCT-116 and HT-29 colon cancer cells with two anti-cancer agents (doxycycline or 3,3'-diindolylmethane) results in profound changes in the intracellular content of several lncRNAs (by up to 100 times). Since many of these RNAs are secreted by tumors into the bloodstream, the obtained results provide a basis for developing more sensitive protocols for serological monitoring of tumor relapse and metastasis, as well as for search of new anti-cancer drugs.

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

The review describes the changes observed in long noncoding RNA (lncRNA) content and function at various stages of carcinogenesis, as well as the prospects of lncRNA application in cancer prognosis.