Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with nearly two million newly diagnosed cases each year. The survival of patients with CRC greatly depends on the cancer stage at the time of diagnosis, with worse prognosis for more advanced cases. Consequently, considerable effort has been directed towards improving population screening programs for early diagnosis and identifying prognostic markers that can better inform treatment strategies. In recent years, long non-coding RNAs (lncRNAs) have been recognized as promising molecules, with diagnostic and prognostic potential in many cancers, including CRC. Although large-scale genome and transcriptome sequencing surveys have identified many lncRNAs that are altered in CRC, most of their roles in disease onset and progression remain poorly understood. Here, we critically review the variety of detection methods and types of supporting evidence for the involvement of lncRNAs in CRC. In addition, we provide a reference catalog that features the most clinically relevant lncRNAs in CRC. These lncRNAs were selected based on recent studies sorted by stringent criteria for both supporting experimental evidence and reproducibility.

Over the last decade the illicit use and abuse of methamphetamine has increased in the United States. Repeated and intermittent use of methamphetamine can lead to sensitization of brain circuits, which can promote continued abuse of methamphetamine. However, neural substrates underlying methamphetamine-induced sensitization are not fully understood. In this proposal, we specifically evaluated the role of kappa opioid receptors (KORs) in the development of methamphetamine-induced sensitization in adult male and female rats. In animals, methamphetamine-induced sensitization manifests as enhanced behavioral response to a dose of methamphetamine after a period of repeated intermittent methamphetamine treatment compared to response to the same dose of methamphetamine prior to exposure to repeated methamphetamine treatment. The experiment was conducted over 28 days and locomotor activity (primary dependent measure) was measured on Days 1, 2, and 28. All animals received saline on Day 1. Animals then received methamphetamine (0.5 mg/kg; i.p.) on Day 2 and Day 28. Animals were treated daily with a single injection of methamphetamine (1 mg/kg; i,p,) for 6 days (Days 3-8; period of repeated intermittent exposure). Animals received no methamphetamine treatment between Days 9-27 (drug-free period). This drug-free period allows for methamphetamine-induced neurobiological changes to take place, which are hypothesized to play a role in the sensitized response to methamphetamine. To assess the role of KOR receptors, animals received a single injection of either the KOR agonist (U50488; 1.5 mg/kg; s.c.) or saline (1 ml/kg; s.c.; control) daily for 6 days (Days 3-8), 30 minutes prior to receiving methamphetamine (1 mg/kg; i.p.). Other groups of animals received either the KOR antagonist (norBNI; 15 mg/kg; s.c.) or saline (1 ml/kg; s.c.; control) on Day 2 after measurement of methamphetamine-induced locomotor activity. Animals received only one injection of the KOR antagonist (norBNI) because of its long duration of action (28 days). Data obtained from the study suggests that activation of the KORs using the KOR agonist (U50488; 1.5 mg/kg; i.p.) significantly decreased methamphetamine-induced sensitization in adult female, but not male rats, compared to respective controls. In contrast, blockade of the KORs using the KOR antagonist (norBNI, 15 mg/kg; s.c.) significantly increased methamphetamine-induced sensitization in adult male, but not female rats, compared to respective controls. Based on the data we can suggest an inhibitory role of KORs in the development of methamphetamine-induced sensitization in adult male rats, which was unmasked by blocking KORs prior to methamphetamine exposure. Together, the data suggest a sex-dependent differential role for KORs in the development of methamphetamine-induced sensitization in adult male and female rats.Dr. D'Souza was supported by an endowed fellowship (Pharmacy Centennial Alumni Chair) and a Bower, Bennett and Bennett summer grant awarded by the

High rates of tobacco smoking are observed in individuals suffering from anxiety or depression. Nicotine is a major psychoactive component of tobacco smoke and previous work has shown that nicotine can produce both anxiolytic‐ and antidepressant‐like effects. Regulators of G protein (RGS) signalling proteins negatively regulate intracellular signaling pathways of neurotransmitters (e.g. adrenaline, dopamine and serotonin), which mediate the antidepressant‐ and anxiolytic‐like effects of nicotine. The objective of the study was to determine the role of the RGS2 and RGS4 in the anxiolytic‐ and antidepressant‐like effects of nicotine. Antidepressant‐ and anxiolytic‐like effects were assessed using the tail suspension model and elevated plus maze, respectively. We used both male and female mice lacking either RGS2 (i.e. RGS2 KO) or RGS4 9i.e. RGS4 KO) and their wildtype counterparts. Both male and female RGS2 KO mice showed anxiolytic effects to nicotine (0.1 mg/kg; i.p., base) compared to respective saline controls. In contrast, no nicotine‐induced (1 mg/kg; i.p., base) antidepressant‐like effects were observed in male and female RGS2 KO mice compared to respective saline controls. Together, these data suggest that RGS2 plays a role in nicotine‐induced anxiolytic effects but not nicotine‐induced antidepressant‐like effects. In contrast, nicotine‐induced antidepressant‐like effects were observed in male RGS4 KO mice, but not female RGS4 KO mice compared to respective saline controls. Also, nicotine‐induced anxiolytic effects were not observed in either male or female RGS4 KO mice. Together, these data suggest that RGS2 and RGS4 differentially mediate nicotine‐induced affective responses. Clinically, these data support a role for targeting these proteins in treating nicotine addiction in patients suffering from comorbid anxiety and/or depression. Support or Funding Information This work was supported by a Bower, Bennett and Bennett grant awarded to Dr. Manoranjan S. D’Souza by the Raabe College of Pharmacy, Ohio Northern University (ONU), Ada, Ohio.