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    Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer
    (AMER PHYSIOLOGICAL SOC, 2020-01-01) Keles, Umur; Iscan, Evin; Yilmaz, Huriye Erbak; Karakulah, Gokhan; Suner, Asli; Bal, Erhan; Tasdemir, Nilgun; Cavga, Ayse Derya; Ekin, Umut; Mutlu, Zeynep; Kahyaoglu, Sila; Serdar, Muhittin A.; Atabey, Nese; Ozturk, Mehmet
    Selective autophagy of the endoplasmic reticulum (ER), namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms: the full-length and the NH2 terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full-length FAM134B is restricted to the brain, testis, spleen, and prostate. In contrast, NH2 terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas, and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. NH2 terminally truncated FAM134B-2 was induced in the liver, skeletal muscle, and heart but not in the pancreas and stomach following starvation. Upon starvation, Fam134b(-/-) mice differed from wild-type mice by less weight loss and less hyperaminoacidemic and hypocalcemic response but increased levels of serum albumin, total serum proteins, and a-amylase. Interestingly, either NH2 terminally truncated FAM134B or both isoforms were downregulated in liver, lung, and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers. NEW \& NOTEWORTHY We reported tissues expressing FAM134B2 such as the kidney, muscle, heart, and pancreas, some of which exhibit stimulated expression upon nutrient starvation. We also demonstrated the effect of Fam134b deletion during ad libitum and starvation conditions. Resistance to weight loss and hypocalcemia, accompanied by an increase in serum albumin and alpha-amylase levels, indicate critical roles of Fam134b in physiology. Furthermore, the differential expression of FAM134B isoforms was shown to be significantly dysregulated in human cancers.
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    Long-term Kinetics of Alpha-fetoprotein in Chronic Hepatitis C Patients Treated with Direct-acting Antivirals and Possible Predictive Role of AFP Response to Treatment on Development of Hepatocellular Carcinoma
    (GALENOS YAYINCILIK, 2021-01-01) Ulasoglu, Celal; Senates, Banu Erkalma; Yapali, Suna; Dumanoglu, Betul; Enc, Feruze; Colak, Yasar; Senates, Ebubekir
    Objectives: To evaluate the post-treatment upto fourth-year kinetics of alpha-fetoprotein (AFP) in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral (DAA) drugs. Materials and Methods: In this retrospective, single-center study, 182 patients (124 female, 58 male) with CHC treated with DAA were included in the study. Biochemistry and AFP were recruited from the hospital database. The data at pre-treatment, 3rd and 48th month after the end of treatment were evaluated. Results: Of the 182 patients, mean age was 58 +/- 12 (28-76), and forty-nine (27\%) had cirrhosis. At month 3, the average decline of AFP was 35.6\% (0.4-97.0). Early decline of AFP <8.7\% was found to be a predictor for HCC development. Mean AFP was 7.7 +/- 9.2 ng/mL at pre-treatment and 3.8 +/- 2.7 at third month (p<0.001). The decline persisted at 48th month (3.6 +/- 2.4 ng/mL). Conclusion: Early decline of AFP and persistence at fourth-year after DAA treatment was observed, except five cases developing HCC. Inadequate decline in AFP level found to be a possible predictor for HCC development. However, these results needs to be confirmed in large-scale multicenter cohorts. This study highlights the importance of AFP response to DAA treatment in identifying HCC risk, especially in patients with cirrhosis.